Oregon Health & Science University

Department of Dermatology

https://www.ohsu.edu/dermatology

Group Leaders

Elizabeth Berry, MD and Sancy Leachman, MD, PhD

Group Members

Elizabeth Berry, MD and Sancy Leachman, MD, PhD

Publications

    • Goldstein AM, Qin R, Chu EY, Elder DE, Massi D, Adams DJ, Harms PW, Robles-Espinoza CD, Newton-Bishop JA, Bishop DT, Harland M, Holland EA, Cust AE, Schmid H, Mann GJ, Puig S, Potrony M, Alos L, Nagore E, Millán-Esteban D, Hayward NK, Broit N, Palmer JM, Nathan V, Berry EG, Astiazaran-Symonds E, Yang XR, Tucker MA, Landi MT, Pfeiffer RM, Sargen MR. Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case series. JAAD Int. 2023 Jan 30;11:43-51. doi: 10.1016/j.jdin.2023.01.013. PMID: 36876055; PMCID: PMC9978843.
    • Slaught C, Berry EG, Bacik L, Skalet AH, Anadiotis G, Tuohy T, Leachman SA. Clinical challenges in interpreting multiple pathogenic mutations in single patients. Hered Cancer Clin Pract. 2021 Feb 4;19(1):15. doi: 10.1186/s13053-021-00172-3. PMID: 33541411; PMCID: PMC7863461.
    • Fuiten AM, Fankhauser RG, Smit DJ, Stark MS, Enright TF, Wood MA, DePatie NA, Pivik K, Sturm RA, Berry EG, Kulkarni RP. Genetic analysis of multiple primary melanomas arising within the boundaries of congenital nevi depigmentosa. Pigment Cell Melanoma Res. 2021
    • Leachman SA, Lucero OM, Sampson JE, Cassidy P, Bruno W, Queirolo P, Ghiorzo P. Identification, genetic testing, and management of hereditary melanoma. Cancer Metastasis Rev. 2017 Mar;36(1):77-90. doi: 10.1007/s10555-017-9661-5. PMID: 28283772; PMCID: PMC5385190.
    • Pho LN, Leachman SA. Genetics of pigmentation and melanoma predisposition. G Ital Dermatol Venereol. 2010 Feb;145(1):37-45. PMID: 20197744.
    • Hansen CB, Wadge LM, Lowstuter K, Boucher K, Leachman SA. Clinical germline genetic testing for melanoma. Lancet Oncol. 2004 May;5(5):314-9. doi: 10.1016/S1470-2045(04)01469-X. PMID: 15120668.
    • Leachman SA, Carucci J, Kohlmann W, Banks KC, Asgari MM, Bergman W, Bianchi-Scarrà G, Brentnall T, Bressac-de Paillerets B, Bruno W, Curiel-Lewandrowski C, de Snoo FA, Debniak T, Demierre MF, Elder D, Goldstein AM, Grant-Kels J, Halpern AC, Ingvar C, Kefford RF, Lang J, MacKie RM, Mann GJ, Mueller K, Newton-Bishop J, Olsson H, Petersen GM, Puig S, Rigel D, Swetter SM, Tucker MA, Yakobson E, Zitelli JA, Tsao H. Selection criteria for genetic assessment of patients with familial melanoma. J Am Acad Dermatol. 2009 Oct;61(4):677.e1-14. doi: 10.1016/j.jaad.2009.03.016. PMID: 19751883; PMCID: PMC3307795.
    • Pho L, Grossman D, Leachman SA. Melanoma genetics: a review of genetic factors and clinical phenotypes in familial melanoma. Curr Opin Oncol. 2006 Mar;18(2):173-9. doi: 10.1097/01.cco.0000208791.22442.09. PMID: 16462187.

Cancer Genetics & Bioinformatics – National University of Mexico

Group Leader

Dr Carla Daniela Robles-Espinoza

Laboratorio Internacional de Investigación sobre el Genoma Humano
Universidad Nacional Autónoma de México, Campus Juriquilla
Blvd. Juriquilla #3001 Col. Jurica La Mesa
C.P. 76230, Querétaro, México
Tel.  +52 55 56 23 43 31 ext. 259

Email: drobles@liigh.unam.mx
http://www.liigh.unam.mx/drobles

Group Members

Irving Simonin Wilmer
Carolina Castañeda García
Omar Isaac García Salinas
Raúl Ossio M.D – PhD student
Patricia Basurto Lozada – student

Research

Our research aims to study how cancer originates and evolves, especially in the context of admixed populations such as Mexican people. Our current focus is melanoma predisposition and progression, with aims to extend to other types of cancer that are prevalent in Latin America. We analyse data from large-scale sequencing methodologies and write software tools to help in its interpretation.

Our on-going projects are:

  • The study of genetic risk variants and mutation drivers in acral melanoma, a poorly studied melanoma subtype that is the most common in Mexico but very rare in European-descent populations. In this project, we are collaborating with Mexico’s National Cancer Institute and the Manuel Gonzalez Gea Hospital to study hundreds of samples collected in these hospitals over three decades.
  • The study of melanoma predisposition genes by exome-sequencing germline DNA from Mexican families and patients. As Mexicans are a highly admixed population, we might identify novel melanoma-predisposing haplotypes that are not found in European-descent populations. In this project, we are collaborating with the National Autonomous University of Mexico’s Clinic of Oncodermatology.
  • The creation of a software tool to easily interpret data from next-generation sequencing technologies in a clinical context.

Publications

Robles-Espinoza CD, Roberts ND, Chen S, Leacy FP, Alexandrov LB, Pornputtapong N, Halaban R, Krauthammer M, Cui R, Timothy Bishop D, Adams DJ (2016). Germline MC1R status influences somatic mutation burden in melanoma. Nat Commun. Jul 12;7:12064. doi: 10.1038/ncomms12064. PMID: 27403562 (See media related to this article)

McIntyre RE, Nicod J, Robles-Espinoza CD, Maciejowski J, Cai N, Hill J, Verstraten R, Iyer V, Rust AG, Balmus G, Mott R, Flint J, Adams DJ (2016). A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice. G3 (Bethesda) May 27. pii: g3.116.030767. doi: 10.1534/g3.116.030767. PMID: 27233670

German Cancer Research Center

Molecular Genetic Epidemiology

Group Leader

Professor Rajiv Kumar
Division of Molecular Genetic Epidemiology
German Cancer Research Center
69120 Heidelberg, Germany
Email: r.kumar@dkfz.de

Group Members

Dr Barbara Heidenreich
Dr Sivaramakrishna Rachakona
Haiying Kong
Evegynia Denisova

Research

The group at the Division of Molecular Genetic Epidemiology has been conducting research on somatic and germline genetics of different cancer with particular emphasis on melanoma and non-melanoma skin cancers.

Melanoma Research

In the field of melanoma our major contribution has been the discovery of mutations in the promoter region of the gene encoding reverse transcriptase catalytic subunit of telomerase. The initial discovery came through study of a multigenerational melanoma pedigree followed by discovery of related somatic mutations. The somatic mutations in the TERT promoter have now been shown to represent major genetic alterations not only in melanoma but also in many different cancers. We have shown that besides being the most common mutations in melanoma, the TERT promoter mutations also associate with markers of poor prognosis, increased growth rate and poor disease free and melanoma specific survival.

The group is an active participant in GENOMEL studies on the role of genetic variants in melanoma susceptibility and survival in melanoma. The group has participated in a number GWAS studies on melanoma and non-melanoma skin cancers.

Publications

  1. Vallarelli AF, Rachakonda PS, André J, Heidenreich B, Riffaud L, Bensussan A, Kumar R, Dumaz N. TERT promoter mutations in melanoma render TERT expression dependent on MAPK pathway activation. Oncotarget. 2016 Jul 16. doi: 10.18632/oncotarget.10634.
  1. Nagore E, Heidenreich B, Rachakonda S, Garcia-Casado Z, Requena C, Soriano V, Frank C, Traves V, Quecedo E, Sanjuan-Gimenez J, Hemminki K, Landi MT, Kumar R. TERT promoter mutations in melanoma survival. Int J Cancer. 2016;139:75-84.
  1. Xie H, Rachakonda PS, Heidenreich B, Nagore E, Sucker A, Hemminki K, Schadendorf D, Kumar R. Mapping of deletion breakpoints at the CDKN2A locus in melanoma: detection of MTAP-ANRIL fusion transcripts. Oncotarget. 2016;7:16490-504.
  1. Vijayakrishnan J, Kumar R, Henrion MY, Moorman AV, Rachakonda PS, Hosen I, da Silva Filho MI, Holroyd A, Dobbins SE, Koehler R, Thomsen H, Irving JA, Allan JM, Lightfoot T, Roman E, Kinsey SE, Sheridan E, Thompson PD, Hoffmann P, Nöthen MM, Heilmann-Heimbach S, Karl-Heinz J, Greaves M, Harrison CJ, Bartram CR, Schrappe M, Stanulla M, Hemminki K, Houlston RS. A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1. Leukemia. 2016 Oct 3. doi: 10.1038/leu.2016.271. [Epub ahead of print]
  1. Willmes C, Kumar R, Becker JC, Fried I, Rachakonda PS, Poppe LM, Hesbacher S, Schadendorf D, Sucker A, Schrama D, Ugurel S. SERPINB1 expression is predictive for sensitivity and outcome of cisplatin-based chemotherapy in melanoma. Oncotarget. 2016;7(9):10117-32. doi: 10.18632/oncotarget.6956.
  1. Espinosa P, Pfeiffer R M, Garcia-Casado Z, Requena C, Landi MT, Kumar R, Nagore E. Risk factors for keratinocyte skin cancer in patients diagnosed with melanoma, a large retrospective study. Eur J Cancer. 2016;53:115-24.
  1. Nagore E, Heidenreich B, Requena C, Casado ZG, Martorell-Calatayud A, Pont-Sanjuan V, Ana JI, Kumar R. TERT promoter mutations associate with fast growing melanoma. Pigment Cell Melanoma Res. 2016;29(2):236-8.
  1. Puig S, Potrony M, Cuellar F, Puig-Butille JA, Carrera C, Aguilera P, Nagore E, Garcia-Casado Z, Requena C, Kumar R, Landman G, Costa Soares de Sá B, Gargantini Rezze G, Facure L, de Avila AL, Achatz MI, Carraro DM, Duprat Neto JP, Grazziotin TC, Bonamigo RR, Rey MC, Balestrini C, Morales E, Molgo M, Bakos RM, Ashton-Prolla P, Giugliani R, Larre Borges A, Barquet V, Pérez J, Martínez M, Cabo H, Cohen Sabban E, Latorre C, Carlos-Ortega B, Salas-Alanis JC, Gonzalez R, Olazaran Z, Malvehy J, Badenas C. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma. Genet Med. 18(7):727-36. doi: 10.1038/gim.2015.160.
  1. Laugier F, Finet-Benyair A, André J, Rachakonda PS, Kumar R, Bensussan A, Dumaz N. RICTOR involvement in the PI3K/AKT pathway regulation in melanocytes and melanoma. Oncotarget. 2015;6(29):28120-31.
  1. Vijayakrishnan J, Henrion M, Moorman AV, Fiege B, Kumar R, Inacio da Silva Filho M, Holroyd A, Koehler R, Thomsen H, Irving JA, Allan JM, Lightfoot T, Roman E, Kinsey SE, Sheridan E, Thompson PD, Hoffmann P, Nöthen MM, Mühleisen TW, Eisele L, Bartram CR, Schrappe M, Greaves M, Hemminki K, Harrison CJ, Stanulla M, Houlston RS. The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A. Sci Rep 2015;5:15065.
  1. Denisova E, Heidenreich B, Nagore E, Rachakonda PS, Hosen I, Akrap I, Traves V, García-Casado Z, López-Guerrero JA, Requena C, Sanmartin O, Serra-Guillén C, Llombart B, Guillén C, Ferrando J, Gimeno E, Nordheim A, Hemminki K, Kumar R. Frequent DPH3 promoter mutations in skin cancers. Oncotarget 2015;6(34):35922-30.
  1. Law MH, Bishop DT, Lee JE, Brossard M, Martin NG, Moses EK, Song F, Barrett JH, Kumar R, Easton DF, Pharoah PD, Swerdlow AJ, Kypreou KP, Taylor JC, Harland M, Randerson-Moor J, Akslen LA, Andresen PA, Avril MF, Azizi E, Scarrà GB, Brown KM, Dȩbniak T, Duffy DL, Elder DE, Fang S, Friedman E, Galan P, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Helsing P, Hočevar M, Höiom V, Ingvar C, Kanetsky PA, Chen WV; GenoMEL Consortium; Essen-Heidelberg Investigators; SDH Study Group; Q-MEGA and QTWIN Investigators; AMFS Investigators; ATHENS Melanoma Study Group, Landi MT, Lang J, Lathrop GM, Lubiński J, Mackie RM, Mann GJ, Molven A, Montgomery GW, Novaković S, Olsson H, Puig S, Puig-Butille JA, Qureshi AA, Radford-Smith GL, van der Stoep N, van Doorn R, Whiteman DC, Craig JE, Schadendorf D, Simms LA, Burdon KP, Nyholt DR, Pooley KA, Orr N, Stratigos AJ, Cust AE, Ward SV, Hayward NK, Han J, Schulze HJ, Dunning AM, Bishop JA, Demenais F, Amos CI, MacGregor S, Iles MM. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma. Nat Genet 2015;47(9):987-95.
  1. Tagliabue E, Fargnoli MC, Gandini S, Maisonneuve P, Liu F, Kayser M, Nijsten T, Han J, Kumar R, Gruis NA, Ferrucci L, Branicki W, Dwyer T, Blizzard L, Helsing P, Autier P, Garcia-Borron JC, Kanetsky PA, Landi MT, Little J, Newton-Bishop J, Sera F, Raimondi S: MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project. British Journal of Cancer 2015;113(2),354-363.
  1. Simon M, Hosen I, Gousias K, Rachakonda S, Heidenreich B, Gessi M, Schramm J, Hemminki K, Waha A, Kumar R. TERT promoter mutations: a novel independent prognostic factor in primary glioblastomas. Neuro Oncol 2015;17(1):45-52.
  1. Hemminki K, Rachakonda S, Musak L, Vymetalkova V, Halasova E, Försti A, Vodickova L, Buchancova J, Vodicka P, Kumar R. Telomere length in circulating lymphocytes: Association with chromosomal aberrations. Genes Chromosomes Cancer 2015;54(3):194-6.
  1. Engström KS, Vahter M, Fletcher T, Leonardi G, Goessler W, Gurzau E, Koppova K, Rudnai P, Kumar R, Broberg K. Genetic variation in arsenic (+3 oxidation state) methyltransferase (AS3MT), arsenic metabolism and risk of basal cell carcinoma in a European population. Environ Mol Mutagen. 2015;56(1):60-9.
  1. Stacey SN, Helgason H, Gudjonsson SA, Thorleifsson G, Zink F, Sigurdsson A, Kehr B, Gudmundsson J, Sulem P, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Fuentelsaz V, Corredera C, Gilaberte Y, Grasa M, Planelles D, Sanmartin O, Rudnai P, Gurzau E, Koppova K, Nexø BA, Tjønneland A, Overvad K, Jonasson JG, Tryggvadottir L, Johannsdottir H, Kristinsdottir AM, Stefansson H, Masson G, Magnusson OT, Halldorsson BV, Kong A, Rafnar T, Thorsteinsdottir U, Vogel U, Kumar R, Nagore E, Mayordomo JI, Gudbjartsson DF, Olafsson JH, Stefansson K. New basal cell carcinoma susceptibility loci. Nat Commun. 2015;6:6825.
  1. Montero I, Requena C, Traves V, García-Casado Z, Kumar R, Nagore E. Age-related characteristics of cutaneous melanoma in a Spanish Mediterranean population. Int J Dermatol. 2015;54(7):778-84.
  1. Pasquali E, García-Borrón JC, Fargnoli MC, Gandini S, Maisonneuve P, Bagnardi V, Specchia C, Liu F, Kayser M, Nijsten T, Nagore E, Kumar R, Hansson J, Kanetsky PA, Ghiorzo P, Debniak T, Branicki W, Gruis NA, Han J, Dwyer T, Blizzard L, Landi MT, Palmieri G, Ribas G, Stratigos A, Council ML, Autier P, Little J, Newton-Bishop J, Sera F, Raimondi S; M-SKIP Study Group. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. Int J Cancer. 2015;136(3):618-31.
  1. Hosen I, Rachakonda PS, Heidenreich B, de Verdier PJ, Ryk C, Steineck G, Hemminki K, Kumar R. Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer. Int J Cancer. 2015;137(7):1621-9.
  1. Heidenreich B, Rachakonda PS, Hosen I, Volz F, Hemminki K, Weyerbrock A, Kumar R. TERT promoter mutations and telomere length in adult malignant gliomas and recurrences. Oncotarget. 2015;6(12):10617-33.
  1. Ibarrola-Villava M, Kumar R, Nagore E, Benfodda M, Guedj M, Gazal S, Hu HH, Guan J, Rachkonda PS, Descamps V, Basset-Seguin N, Bensussan A, Bagot M, Saiag P, Schadendorf D, Martin-Gonzalez M, Mayor M, Grandchamp B, Ribas G, Nadem S. Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition. Int J Cancer. 2015;136(9):2109-19.
  1. García-Casado Z, Traves V, Bañuls J, Niveiro M, Gimeno-Carpio E, Jimenez-Sanchez AI, Moragón M, Onrubia JA, Oliver V, Kumar R, Nagore E. BRAF, NRAS and MC1R status in a prospective series of primary cutaneous melanoma. Br J Dermatol. 2015;172(4):1128-31.
  1. Hosen I, Rachakonda PS, Heidenreich B, Sitaram RT, Ljungberg B, Roos G, Hemminki K, Kumar R. TERT promoter mutations in clear cell renal cell carcinoma. Int J Cancer. 2015;136(10):2448-52.
  1. Nagore E, Heidenreich B, Rachakonda S, Garcia-Casado Z, Requena C, Soriano V, Frank C, Traves V, Quecedo E, Sanjuan-Gimenez J, Hemminki K, Teresa Landi M, Kumar R. TERT promoter mutations in melanoma survival. Int J Cancer. 2016;139(1):75-84. doi: 10.1002/ijc.30042.
  1. Hu HH; Kannengiesser C; Lesage S; Andre J; Mourah S; Michel L; Descamps V; Basset- Seguin N; Bagot M; Bensussan A; Lebbé C; Deschamps L; Saiag P; Leccia MT; Tsalamlal A; Kumar R; Klebe S; Grandchamp B; Andrieu-Abadie  N; Thomas L; Brice A; Nicolas Dumaz N; Soufir N. PARKIN inactivation link Parkinson’s disease to melanoma. J Natl Cancer Inst. 2015;108(3).
  1. Xie H, Rachakonda PS, Heidenreich B, Nagore E, Sucker A, Hemminki K, Schadendorf D, Kumar R. Mapping of deletion breakpoints at the CDKN2A locus in melanoma: detection of MTAP-ANRIL fusion transcripts. Oncotarget. 2016 Feb 19. doi: 10.18632/oncotarget.7503.
  1. Heidenreich B, Nagore E, Rachakonda PS, Garcia-Casado G, Requena C, Traves V, Becker J, Soufir N, Hemminki K, Kumar R. Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma. Nat Commun. 2014 Feb 26;5:3401. doi: 10.1038/ncomms4401.
  1. Davies JR, Jewell R, Affleck P, Anic GM, Randerson-Moor J, Ozola A, Egan KM, Elliott F, García-Casado Z, Hansson J, Harland M, Höiom V, Jian G, Jönsson G, Kumar R, Nagore E, Wendt J, Olsson H, Park JY, Patel P, Pjanova D, Puig S, Schadendorf D, Rachakonda PS, Snowden H, Stratigos AJ, Bafaloukos D, Ogbah Z, Sucker A, Van den Oord JJ, Van Doorn R, Walker C, Okamoto I, Wolter P, Barrett JH, Bishop DT, Newton-Bishop J.Inherited variation in the PARP1 gene and survival from melanoma. Int J Cancer. 2014 Feb 18. doi: 10.1002/ijc.28796.
  1. Heidenreich B, Rachakonda PS, Hemminki K, Kumar R. TERT promoter mutations in cancer development. Current Opinion in Genetics and Development, 2014; 24:30-37.
  1. Stacey SN, Sulem P, Gudbjartsson DF, Jonasdottir A, Thorleifsson G, Gudjonsson SA, Masson G, Gudmundsson J, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Fuentelsaz V, Corredera C, Grasa M, Planelles D, Sanmartin O, Rudnai P, Gurzau E, Koppova K, Hemminki K, Nexø BA, Tjønneland A, Overvad K, Johannsdottir H, Helgadottir HT, Thorsteinsdottir U, Kong A, Vogel U, Kumar R, Nagore E, Mayordomo JI, Rafnar T, Olafsson JH, Stefansson K. Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma. Hum Mol Genet. 2014;23(11):3045-53. PMID: 24403052
  1. Blank S, Rachakonda S, Keller G, Weichert W, Lordick F, Langer R, Springfeld C, Bruckner T, Becker K, Kumar R, Ott K. retrospective comparative exploratory study on two Methylentetrahydrofolate Reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients. BMC Cancer. 2014;14(1):58.
  1. Peña-Vilabelda MM, García-Casado Z, Requena C, Traves V, López-Guerrero JA, Guillén C, Kumar R, Nagore E. Clinical Characteristics of Patients With Cutaneous Melanoma According to Variants in the Melanocortin 1 Receptor Gene. Actas Dermosifiliogr. 2014;105:159-71.
  1. Davies JR, Field S, Randerson-Moor J, Harland M, Kumar R, Anic GM, Nagore E, Hansson J, Höiom V, Jönsson G, Gruis NA, Park JY, Jian G, Rachakonda PS, Wendt J, Pjanova D, Puig S, Schadendorf D, Okamoto I, Olsson H, Affleck P, García-Casado Z, Puig-Butille JA, Stratigos AJ, Kodela E, Donina S, Sucker A, Hosen I, Egan KM, Barrett JH, van Doorn R, Bishop DT, Newton-Bishop J. An inherited variant in the gene coding for vitamin D binding protein and survival from cutaneous melanoma: a BioGenoMEL study. Pigment Cell Melanoma Res. 2014; 27:234-43.
  1. Rachakonda PS, Hosen I, de Verdier PJ, Fallah M, Heidenreich B, Ryk C, Wiklund NP, Steineck G, Schadendorf D, Hemminki K, Kumar R. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc Natl Acad Sci U S A. 2013;110:17426-31.
  1. Migliorini G, Fiege B, Hosking FJ, Ma Y, Kumar R, Sherborne AL, da Silva Filho MI, Vijayakrishnan J, Koehler R, Thomsen H, Irving JA, Allan JM, Lightfoot T, Roman E, Kinsey SE, Sheridan E, Thompson P, Hoffmann P, Nöthen MM, Mühleisen TW, Eisele L, Zimmermann M, Bartram CR, Schrappe M, Greaves M, Stanulla M, Hemminki K, Houlston RS. Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype. Blood. 2013;122:3298-307.
  1. Maccioni L, Rachakonda PS, Bermejo JL, Planelles D, Requena C, Hemminki K, Nagore E, Kumar R. Variants at the 9p21 locus and melanoma risk. BMC Cancer. 2013;13:325.
  1. Dutruel C, Bergmann F, Rooman I, Zucknick M, Weichenhan D, Geiselhart L, Kaffenberger T, Rachakonda PS, Bauer A, Giese N, Hong C, Xie H, Costello JF, Hoheisel J, Kumar R, Rehli M, Schirmacher P, Werner J, Plass C, Popanda O, Schmezer P. Early epigenetic downregulation of WNK2 kinase during pancreatic ductal adenocarcinoma development. Oncogene. 2014; 33(26):3401-10. doi: 10.1038/onc.2013.312
  1. Puig-Butillé JA, Carrera C, Kumar R, Garcia-Casado Z, Badenas C, Aguilera P, Malvehy J, Nagore E, Puig S. Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with Lentigo Maligna Melanoma in a Mediterranean population. Br J Dermatol. 2013; 169:804-11
  1. Surdu S, Fitzgerald EF, Bloom MS, Boscoe FP, Carpenter DO, Haase RF, Gurzau E, Rudnai P, Koppova K, Févotte J, Vahter M, Leonardi G, Goessler W, Kumar R, Fletcher T. Occupational Exposure to Ultraviolet Radiation and Risk of Non-Melanoma SkinCancer in a Multinational European Study. PLoS ONE 8(4): e62359. doi:10.1371/journal.pone.0062359
  1. Surdu S, Fitzgerald EF, Bloom MS, Boscoe FP, Carpenter DO, Haase RF, Gurzau E, Rudnai P, Koppova K, Févotte J, Vahter M, Leonardi G, Goessler W, Kumar R, Fletcher T. Occupational exposure to arsenic and risk of non-melanoma skin cancer in a multinational European study. Int J Cancer. 2013; 133:2182-91.
  1. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science. 2013; 339:959-61.
  1. Rachakonda S, Bauer A, Xie H, Campa D, Rizzato C, Canzian F, Beghelli S, Greenhalf W, Costello E, Schanne M, Heller A, Scarpa A, Neoptolemos JP, Werner J, Buchler M, Hoheisel J, Hemminki K, Giese N, Kumar R. Somatic Mutations in Exocrine Pancreatic Tumors: Association with Patient Survival. PLoS ONE. 2013;8(4): e60870.
  1. Maccioni L, Rachakonda PS, Scherer D, Bermejo JL, Planelles D, Requena C, Hemminki K, Nagore E, Kumar R. Variants at chromosome 20 (ASIP locus) and melanoma risk. Int J Cancer. Int J Cancer. 2013;132:42-54
  1. Lenci RE, Bevier M, Brandt A, Bermejo JL, Sucker A, Moll I, Planelles D, Requena C, Nagore E, Hemminki K, Schadendorf D, Kumar R. Influence of genetic variants in type I interferon genes on melanoma survival and therapy. PLoS One. 2012;7(11):e50692. doi: 10.1371/journal.pone.0050692.
  1. Slyskova J, Korenkova V, Collins AR, Prochazka P, Vodickova L, Svec J, Lipska L, Levy M, Schneiderova M, Liska V, Holubec L, Kumar R, Soucek P, Naccarati A, Vodicka P. Functional, genetic and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas. Clin Cancer Res. 2012;18:5878-87.
  1. Canelas MM, Bermejo JL, Landi MT, Requena C, Guillen C, Kumar R, Nagore E. Characterization of nonacral melanoma patients without typical risk factors. Melanoma Res. 2012;22:316-9.
  1. Raimondi S, Gandini S, Fargnoli MC, Bagnardi V, Maisonneuve P, Specchia C, Kumar R, Nagore E, Han J, Hansson J, Kanetsky PA, Ghiorzo P, Gruis NA, Dwyer T, Blizzard L, Fernandez-de-Misa R, Branicki W, Debniak T, Morling N, Landi MT, Palmieri G, Ribas G, Stratigos A, Cornelius L, Motokawa T, Anno S, Helsing P, Wong TH, Autier P, García-Borrón JC, Little J, Newton-Bishop J, Sera F, Liu F, Kayser M, Nijsten T, Study Group G. Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies. BMC Med Res Methodol. 2012;12:116.
  1. Davies JR, Randerson-Moor J, Kukalizch K, Harland M, Kumar R, Madhusudan S, Nagore E, Hansson J, Höiom V, Ghiorzo P, Gruis NA, Kanetsky PA, Wendt J, Pjanova D, Puig S, Saiag P, Schadendorf D, Soufir N, Okamoto I, Affleck P, García-Casado Z, Ogbah Z, Ozola A, Queirolo P, Sucker A, Barrett JH, van Doorn R, Bishop DT, Newton-Bishop J. Inherited variants in the MC1R gene and survival from cutaneous melanoma: a BioGenoMEL study. Pigment Cell Melanoma Res. 2012;25:384-94.
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  1. Martino A, Campa D, Buda G, Sainz J, García-Sanz R, Jamroziak K, Reis RM, Weinhold N, Jurado M, Ríos R, Szemraj-Rogucka Z, Marques H, Szemraj J, Stein A, Kumar R, Orciuolo E, Gemignani F, Landi S, Goldschmidt H, Petrini M, Dumontet C, Canzian F, Rossi AM. Polymorphisms in xenobiotic transporters ABCB1, ABCG2, ABCC2, ABCC1, ABCC3 and multiple myeloma risk: a case-control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium. Leukemia. 2012;26:1419-22.

The Wistar Institute Melanoma Research Centre

Wistar Institute
3601 Spruce Street, Room 472
Philadelphia, PA 19104
Information: Jessica L. Kohn, jkohn@wistar.org
215-495-6883

Group Leader

Dr Meenhard Herlyn
Caspar Wistar Professor in Melanoma Research
Director, The Wistar Institute Melanoma Research Centre
Professor, Molecular and Cellular Oncogenesis Program
meenhard-2016

Group Members

Dr. Mizuho Kalabis, Research Assistant Professor
Dr. Clemens Krepler, Research Assistant Professor
Dr. Shyam Somasundaram, Research Assistant Professor
Dr. Gao Zhang, Staff Scientist
Dr. Jianglan Liu, Associate Staff Scientist
Trish Brafford, Wistar Research Assistant
Dr. Ling Li, Wistar Research Assistant
Katrin Sproesser, Wistar Research Assistant
Marilda Beqiri, Research Assistant III
Josh Wang, Research Assistant II
Min Xiao, Research Assistant IV
Brian Gavin, Technician II
Jessica L. Kohn, Laboratory Coordinator

Research

Dr. Meenhard Herlyn’s laboratory at The Wistar Institute focuses on the biology that underlies melanoma, the most aggressive form of skin cancer. His efforts have pioneered the use of the three-dimensional “artificial skin” cultures to study the behavior of both tumor and normal cells that sustain tumor growth, a system known as the tumor microenvironment. The Herlyn Laboratory has transformed the scientific understanding of stem cells as they relate to cancer, and their work on the networks of signaling pathways in melanoma has formed the basis of numerous therapies now in clinical trials or very recently approved.

The ability to model the microenvironment of normal and diseased human tissue through 3-D artificial skin provides the Herlyn Laboratory with a unique insight into cancer research. Growing cells in these tissue-like models induces major changes in gene expression similar to those in animals and patients, making them superbly suited for studies of signaling between normal and malignant cells, tumor formation, and drug resistance. These models also make a unique testing ground for ideas on future therapeutics and drug combinations.

The Herlyn Laboratory also seeks to further define the various signaling pathways that work in cancer cells in order to discover new opportunities to inhibit cancer growth through targeted therapeutics. Since therapy is increasingly guided by the genetic aberrations in tumors, Dr. Herlyn and his colleagues are developing combinations of compounds that take into account the genetic signature of tumors, with the specific goal of individualized cancer therapy. Currently, the Herlyn Laboratory collaborates with pharmaceutical companies as well as academic chemists and structural biologists to select and further develop compounds for tumor inhibition. Tumor heterogeneity, i.e., the differences between cells within one tumor, among different tumor lesions of the same patient, or between patients even if the tumors are of similar genetic signatures, provides major challenges for future therapy. The laboratory is developing biological signatures of melanoma cells that take into account the various forms of heterogeneity.

Another major effort of the Herlyn Laboratory is the study of therapy resistance and tumor dormancy. Tumor cells can become dormant in primary tumors or at any time after metastatic dissemination and can persist in the dormant state for many years, allowing tumors to resist treatment. Dr. Herlyn’s working hypothesis is that defined tumor subpopulations are central to dormancy and drug resistance due to their slow turnover and their non-responsiveness to growth signals. His efforts seek to define how tumor cells escape dormancy for growth, invasion, and metastasis, and how to best develop strategies for therapy.

 

Publications

Shannan B, Chen Q, Watters A, Perego M, Krepler C, Thombre R, Li L, Rajan G, Peterson S, Gimotty PA, Wilson M, Nathanson KL, Gangadhar TC, Schuchter LM, Weeraratna AT, Herlyn M, Vultur A. Enhancing the evaluation of PI3K inhibitors through 3D melanoma models. Pigment Cell Melanoma Res. 2016;29:317-28. PMID26850518 (PMCID4840066)

Krepler C, Xiao M, Sproesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos PI, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized preclinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res. 2016;22:1592-602. PMID26673799 (PMCID4818716)

Brafford P, Sproessor K, Krepler C, Herlyn M. 1205Lu is human melanoma depending on the source. J Cancer Sci Ther. 2016;8:113.

Lu H, Liu S, Zhang G, Kwong LN, Zhu Y, Miller JP, Hu Y, Zhong W, Zeng J, Wu L, Krepler C, Sproesser K, Xiao M, Xu W, Karakousis GC, Schuchter LM, Field J, Zhang PJ, Herlyn M, Xu X, Guo W. Oncogenic BRAF-mediated melanoma cell invasion. Cell Rep. 2016;15:2012-24. PMID27210749 (PMCID4889462)

Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Xu W, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, Herlyn M. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. 2016;126:1834-56. PMID27043285 (PMCID4855947)

McNeal AS, Liu K, Nakhate V, Natale CA, Duperret EK, Capell BC, Dentchev T, Berger SL, Herlyn M, Seykora JT, Ridky TW. CDKN2B Loss Promotes Progression from Benign Melanocytic Nevus to Melanoma. Cancer Discov. 2015;5(10):1072-85. PMID26183406 PMCID4592422

Wang YJ, Herlyn M. The emerging roles of Oct3 in tumor-initiating cells. Am J Physiol Cell Physiol. 2015;309(11):C709-18. PMID26447206

Krepler C, Xiao M, Spoesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos P, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized pre-clinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res. 2015 Dec 16 [Epub ahead of print]. PMID26673799

Ravindran Menon D, Das S, Krepler C, Vultur A, Rinner B, Schauer S, Kashofer K, Wagner K, Zhang G, Bonyadi Rad E, Haass NK, Soyer HP, Gabrielli B, Somasundaram R, Hoefler G, Herlyn M, Schaider H. A stress-induced early innate response casues multidrug tolerance in melanoma. Oncogene. 2015;34(34):4448-59. PMID25417704; PMCIDPMC4442085.

Joshi S, Wels C, Beham-Schmid C, Fukunaga-Kalabis M, Holmen SL, Otte M, Herlyn M, Waldhoer M, Schaider H. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. Int J Cancer. 2015;137:1503-8. PMID25754407, PMC4496263

Cierlitza M, Chauvistre H, Bogeski I, Zhang X, Hauschild A, Herlyn M, Schadendorf D, Vogt T, Roesch A. Mitochondiral oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma subpopulations. Exp Dermatol. 2015;24:155-157. PMID25453510

Kraya AA, Piao S, Xu X, Zhang G, Herlyn M, Gimotty P, Levine B, Amaravadi RK, Speicher DW. Identification of secreted proteins that reflect autophagy dynamics within tumor cells. Autophagy. 2015;11:60-74. PMID25484078

Webster MR, Xu M, Kinzler KA, Kaur A, Appleton J, O’Connell MP, Marchbank K, Valiga A, Dang VM, Perego M, Zhang G, Slipicevic A, Keeney F, Lehrmann E, Wood W 3rd, Becker KG, Kossenov AV, Frederick DT, Flaherty KT, Xu X, Herlyn M, Murphy ME, Weeraratna AT. Wnt5a promotes and adaptive, senescence-like stress stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res. 2015;28:184-195. PMID25407936

Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drablos F, Lennartsson, A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi A, Arner A, Axton R, Baillie JK, Beckhouse A, Bodega B, Briggs J, Brombacher F, Davis M, Detmar M, Ehrlund A, Endoh M, Eslami A, Fagiolini M, Fairbairn L, Faulkner GJ, Ferrai C, Fisher ME, Forrester L, Goldowitz D, Guler R, Ha T, Hara M, Herlyn M, Ikawa T, Kai C, Kawamoto H, Khachigian L, Klinken PS, Kojima S, Koseki H, Klein S, Mejhert N, Miyaguchi K, Mizuno Y, Morimoto M, Morris KJ, Mummery C, Nakachi Y, Ogishima S, Okada-Hatakeyama M, Okazaki Y, Orlando Y, Ovchinnikov D, Passier R, Patrikakis M, Pombo A, Qin XY, Roy S, Sato H, Savvi S, Saxena A, Schwegmann A, Sugiyama D, Swoboda R, Tanaka R, Tomoiu A, Winteringham LN, Wolvetang E, Yanagi-Mizuochi C, Yoneda M, Zabierowski S, Zhang P, Abugessaisa I, Bertin N, Diehl AD, Fukuda S, Furuno M, Harshbarger J, Hasegawa A, Hori F, Ishikawa-Kato S, Ishizu Y, Itoh M, Kawashima T, Kojima M, Kondo N, Lizio M, Meehan TF, Mungall CJ, Murata M, Nishiyori-Sueki H, Sahin S, Sato-Nagao S, Severin J, de Hoon MJL, Kawai J, Kasukawa T, Lassmann T, Suzuki H, Kawaji H, Summers KM, Wells C, Hume DA, Forrest ARR, Sandelin A, Carninci P, Hayashizaki Y. Gene regulation; transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science. 2015;347:1010-4. PMID25678556

Slipicevic A, Herlyn M. KIT in melanoma: Many shades of grey. J Invest Dermatol. 2015;135:337-8. PMID25573046

Wang T, Xiao M, Ge Y, Krepler C, Belser E, Lopez-Coral A, Xu X, Zhang G, Azuma R, Liu Q, Liu R, Li L, Amaravadi RK, Xu W, Karakousis G, Gangadhar TC, Schuchter LM, Lieu M, Khare S, Halloran MB, Herlyn, M, Kaufman, R. BRAF inhibition stimulates melanoma-associated macrophages to drive tumor growth. Clin Cancer Res. 2015;21:1652-1664. PMID25617424

Joshi S, Wels C, Beham-Schmid C, Fukunaga-Kalabis M, Holmen SL, Otte M, Herlyn M, Waldhoer M, Schaider H. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. Int J Cancer. [Epub ahead of print, 6 Mar. 2015] PMID25754407

Fukunaga-Kalabis M, Hristova DM, Wang JX, Li L, Heppt MV, Wei Z, Gyurdiev A, Webster MR, Oka M, Weeraratna AT, Herlyn M. UV-induced Wnt7a in the human skin microenvironment specifies the fate of neural crest-like cells via suppression of Notch. J Invest Dermatol. 2015;135:1521-1532. PMID25705850

Liang C; FANTOM Consortium [….Herlyn M….], Forrest AR, Wagner GP. The statistical geometry of transcriptome divergence in cell-type evolution and cancer. Nat Comm. 2015;6:6066. PMID25585899

Yoshihara M, Ohmiya H, Hara S, Kawasaki S, FANTM consiortium […Herlyn M….], Hayashuzaki, Y, Itoh M, Kawaji H, Tsujikawa M, Nishida K. Discovery of molecular markers to discriminate corneal endothelial cells in the human body. PLoS One. 2015;10(3):e0117581. PMID25807145

Liu S, Tetzlaff MT, Wang T, Yang R, Xie L, Zhang G, Krepler C, Xiao M, Bequiri M, Xu W, Karakousis G, Schuchter L, Amaravadi RK, Xu W, Wei Z, Herlyn M, Yao, Y, Zhang L, Wang Y, Zhang K. Xu X. miR-200c/Bmi1 axis and epithelial-mesenchymal transition contribute to acquire resistance to BRAF inhibitor treatment. Pigment Cell Melanoma Res. 2015;28:431-41. PMID25903073

Kim H, Frederick DT, Levesque MP, Cooper ZA, Fang Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn M, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai ZA. Downregulation of the ubiquitin ligase RNF125 underlies resistance of melanoma cells to BRAF inhibitors via JAK1 deregulation. Cell Rep. 2015;11:1458-73. PMID26027934

Vultur A, Smalley K, Herlyn M. Melanoma. In: Gelman EP, Sawyer CL, Rauscher III FJ, eds. Molecular Oncology: Causes of Cancer and Targets for Treatment. West Nyack, NY: Cambridge University Press; 2014:698-703.

Wang T, Ge Y, Xiao M, Lopez-Coral A, Li L, Roesch A, Huang C, Alexander P, Vogt T, Xu X, Hwang W-T, Lieu M, Belser E, Liu R, Somasundaram R, Herlyn M, Kaufman RE. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol. 2014;134:1108-1118. PMID24157461

Nallet-Staub F, Marsaud V, Li L, Gilbert C, Dodier S, Bataille V, Sudol M, Herlyn M, Mauviel A. Pro-invasive activity of the hippo pathway effectors YAP and TAZ in cutaneous melanoma. J Invest Dermatol. 2014;134:123-132. PMID23897276

Vultur A, Villanueva J, Krepler C, Rajan G, Chen Q, Li L, Gimotty P, Wilson M, Hayden J, Keeney F, Nathanson KL, Herlyn M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene. 2014;33:1850-1861. PMID23624919 (PMC3769503)

Geserick P, Herlyn M, Leverkus M. On the TRAIL to overcome BRAF-inhibitor resistance. J Invest Dermatol. 2014;134:315-8. PMID24424456

Ma X-H, Pioa S-F, Dey S, Mcafee Q, Karakousis G, Villanueva J, Hart LS, Levi S, Hu J, Zhang G, Lazova R, Klump V, Pawelek JM, Xu X, Schuchter LM, Davies MA, Herlyn M, Winkler J, Koumenis C, Amaravadi RK. Targeting ER stress induced autophagy overcomes resistance to BRAF inhibition in melanoma. J Clin Invest. 2014;124:1406-1417. PMID24569374

Peng H, Talebzadeh-Farrooji M, Osborne MJ, Prokop JW, McDonald PC, Karar J, Hou Z, He M, Kebebew E, Orntoft T, Herlyn M, Caton AJ, Fredericks W, Malkowicz B, Paterno CS, Carolin AS, Speicher DW, Skordalakes E, Huang Q, Dedhar S, Borden KL, Rauscher FJ 3rd. LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that regulates cell motility and tumor progression by directly binding to and activating the integrin-linked kinase. Cancer Res. 2014;74:1390-1403. PMID24590809

Arner E, Forrest AR, Ehrlund A, Mejhert N, Itoh M, Kawaji H, Lassmann T, Laurencikiene J, Rydén M, Arner P, FANTOM Consortium (…Herlyn M…). Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells. PLoS One. 2014;9(3):e80274. PMID24676332

Hasegawa Y, Tang D, Takahashi N, Hayashizah Y, Forrest AR, FANTOM Consortium (…Herlyn M…), Suzuki H. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes. Sci Rep. 2014;4:5228. PMID24957798

Yang R, Zhend Y, Li L, Liu S, Spata M, Wei Z, Nace A, Herlyn M, Cui R, Guo W, Cotsarelis G, Xu X. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors. Nat Comm. 2014;5:5807. PMID25510211

Ravindran Menon D, Das S, Krepler C, Vultur A, Rinner B, Schauer S, Kashofer K, Wagner K, Zhang G, Rad BE, Hass N, Soyer P, Gabrielli B, Somasundaram R, Hoefler G, Herlyn M, Schaider H. A stress-induced early innate response causes multi-drug tolerance in melanoma. Oncogene. 2014;1-12. PMID25619837

Slipicevic A, Somasundaram S, Sproesser K, Herlyn M. Isolation of melanoma subpopulations using negative selection. Methods Mol Biol. 2014;1102:501-512. PMID24258995

Liu J, Fukunaga-Kalabis M, Li L, Herlyn M. Developmental pathways activated in melanocytes and melanoma. Arch Biochem Biophys. 2014;563C:13-21. PMID25109840

Zhang G, Herlyn M. Linking SOX10 to slow-growth resistance phenotype. Cell Res. 2014;24:906-907. PMID24853952

Somasundaram R, Herlyn M. Indomethacin to the rescue of TRAIL-resistant melanomas. J Invest Dermatol. 2014;134:1198-1199. PMID24732334

Andersson R, Gebhard C,Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Müller F; FANTOM Consortium (…Herlyn M…), Forrest AR, Carninci P, Rehli M, Sandelin A. An atlas of active enhancers across human cell types and tissues. Nature. 2014;27;507(7493):455-61. PMID24670763

Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nagao-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest AR, Standley, DM, Date H, Sakaguchi S; FANTOM Consortium (…Herlyn M…). Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proc Natl Acad Sci USA. 2014;111:5289-5294. PMID24706905

Hayashizaki Y, Forrest A, Kawaji H, Rehli M, Baillie J, de Hoonn M, Haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson R, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto M, Vitezic M, Severin J, Semple C, Ishizu Hayashizaki Y, Forrest A, Kawaji H, Rehli M, Baillie J, de Hoonn M, haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson R, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto M, Vitezic M, Severin J, Semple C, Ishizu Y, Kaiho A, Saka A, Hasegawa A, Knox A, Mackay-Sim A, Edge A, Bonetti A, Diehl A, Favorov A, Meynert A, Saxena A, Joshi A, Califano A, Lennartsson A, Gibson A, Kwon A, Schwegmann A, Beckhouse A, Mathelier A, Blumenthal A, Sajantila A, Pain A, Kasianov A, Kubosaki A, Manabe R, Bodega B, Marchand B, Jankovich B, Cannistraci CV, Davis C, Furlanello C, Plessy C, Kai C, Schmidl C, Wells C, Mummery C, Schneider C, Sugiyama D, Goldowitz D, de Lima Morais D, Albanese D, Vijayan D, Ovchinnikov D, Valen E, Dalla E, Wood E, Saijyo E, Schultes E, van Nimwegen E, Wolvetangg E, Drabløs D, Brombacher F, Hori F, Nakahara F, Altschuler G, Faulkner G, Jurman G, Schulze-Tanzil G, Sheng G, Fang H, Clevers H, Koseki H, Persson H, Enomoto H, Tatsukawa H, Sato H, Ohmiya H, Morikawa H, Nishiyori H, Satoh H, Toyoda H, Kawamoto H, Ohno H, Tanaka H, Carbajo D, Shimoji H, Motohashi H, Jia H, Hoof I, Vorontsov I, Alam I, Briggs J, Prendergast J, Shin J, Harshbarger J, Laros J, Mar J, Archer J, Ramilowski J, Blake J, Kempfle J, Kere J, Gough J, Takai J, Furusawa J, Li K, Kaida K, Ekwall K, Kajiyama K, Moro K, Iida K, Hitchens K, Nakazato K, Summers K, Lipovich L, Khachigian L, Winteringham L, Huminiecki L, Babina M, Fisher M, Rashid M, van de Wetering M, Chierici M, Roncador M, Patrikakis M, Okada-Hatakeyama M, Thompson M, Frith M, Farach-Carson M, Furuno M, Hamaguchi M, Suzuki M, Yamamoto M, Harbers M, Edinger M, Burroughs AM, Herlyn M, Detmar M, Fagiolini M, Tagami M, Kojima M, Yoneda M, Endoh M, Ohshima M, Hara M, Morimoto M, Murata M, Sakai M, Rye M, Kanamori-Katayama M, Ohkura N, Takahashi N, Kondo N, Mejhert N, Ninomiya N, Hofmann O, Rackham O, Rizzu P, ‘t Hoen P, Arner P, Zhang P, Klinken P, Balwierz P, Guler R, Fujita R, Passier R, Verardo R, Swoboda R, Kato S, Baker S, Krampitz S, Nagao-Sato S, Ho Sui S, Yoshida S, Koyasu S, Sakaguchi S, Katayama S, Fukuda S, Noma S, Watanabe S, Kawaguchi S, Piazza S, Zucchelli S, Kojima S, Ogishima S, Gustincich S, Roy S, Zabierowski S, Savvi S, Guhl S, Pradhan Bhatt S, Nozaki T, Dohi T, Sugiyama T, Hashimoto T, Toyoda T, Geijtenbeek T, Sengstag T, Gingeras T, Ha T, Ravasi T, Ikawa T, Kenna T, Kitamura T, Nakamura T, Kawashima T, Orlando V, Lee W, Wasserman W, Zhao W, Ciani Y, Okazaki Y, Shimoni Y, Yonekura Y, Yamaguchi Y, Mizuno Y, Hasegawa Y, Kawamura Y, Nakamura Y, Chen Y, Nakachi Y, Tatum Z, Suzuki H, Daub C, Kawai J, Heutink P, Hide W, Lenhard B, Bajic V, Makeev V, Sandelin A, Hume D, Carninci P, van den Berg L, Fairbairn L, Kaczkowski B, Lilje B, Simon C, Motakis E, Kasukawa T, Arakawa T, Suzuki N, Young R. A promoter level mammalian expression atlas. Nature. 2014;507:462-470. PMID24670764

Somasundaram R, Herlyn M. Relapse of melanoma after successful adoptive T-cell therapy: escape through inflammation-induced phenotypic melanoma plasticity. Pigment Cell Melanoma Res. 2013;26:2-4.

Balaburski GM, Leu JI, Beeharry N, Hayik S, Andrake MD, Zhang G, Herlyn M, Villanueva J, Dunbrack RL, Yen T, George DL, Murphy ME. A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res. 2013;11:219-229.

Krepler C, Chunduru SK, Halloran MB, He X, Xiao M, Vultur A, Villanueva J, Mitsuuchi Y, Neiman EM, Benetatos C, Nathanson KL, Amaravadi RK, Pehamberger H, McKinlay M, Herlyn M. The novel SMAC inhibitor birinapant exhibits potent activity against human melanoma cells. Clin Cancer Res. 2103;19:1784-1794.

Wang T, Somasundaram R, Herlyn M. Combination therapy of immunocytokines with Ipilimumab: a cure for melanoma? J Invest Dermatol. 2013;133(3):595-596.

Li L, Fukunaga-Kalabis M, Herlyn M. Isolation, characterization, and differentiation of human multipotent dermal stem cells. Methods Mol Biol. 2013;989:235-246.

Swoboda R, Herlyn M. There is a world beyond protein mutations: the role of non-coding RNAs in melanomagenesis. Exp Dermatol. 2013;22:303-306.

Wang T, Herlyn M. The macrophage: a new factor in UVR-induced melanomagenesis. J Invest Dermatol. 2013;133:1711-1713.

Vultur A, Herlyn M. Snapshot: melanoma. Cancer Cell. 2013;23:706.

Merlino G, Flaherty K, Acquavella N, Day CP, Aplin A, Homen S, Topalian S, Van Dyke T, Herlyn M. The future of preclinical mouse models in melanoma treatment is now. Pigment Cell Melanoma Res. 2013;26:E8-E14.

Kastl A, Dieckman S, Wähler K, Völker T, Kastl L, Shannan B, Harms K, Ocker M, Parak W, Herlyn M, Meggers E. Rhenium complexes with visible-light-induced anticancer activity. Organometallic Med Chem. 2013;8:924-927.

Desai BM, Villanueva J, Nguyen T-TK, Lioni M, Xiao M, Kong J, Krepler C, Vultur A, Flaherty KT, Nathanson KL, Smalley KSM, Herlyn M. The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One. 2013;8(3):e59588.

Vultur A, Villanueva J, Krepler C, Rajan G, Chen Q, Li L, Gimotty P, Wilson M, Hayden J, Keeney F, Nathanson KL, Herlyn M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene. 2013;33:1850-61. PMID23624919 (PMCID3769503)

Aird KM, Zhang G, Li H, Tu Z, Bitler BG, Garipov A, Wu H, Wei Z, Wagner SN, Herlyn M, Zhang R. Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell Rep. 2013;3:1-4.

Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, Körbel C, Laschke MW, Gimotty PA, Philipp SE, Krause E, Pätold S, Villanueva J, Krepler C, Fukunaga-Kalabis M, Hoth M, Bastian B, Vogt T, Herlyn M. Overcoming intrinsic multi-drug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer Cell. 2013;23:811-825.

Reuveni H, Flashner-Abramson E, Steiner L, Makedonski K, Song R, Shir A, Herlyn M, Bar-Eli M, Levitzki A. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res. 2013;73:4383-4394.

Kwak J, Gallagher M, Ozdener MH, Wysocki CJ, Goldsmith BR, Isamah A, Faranda A, Fakharzadeh SS, Herlyn M, Johnson ATC, Preti G. Volatile biomarkers from human melanoma cells. J Chromatography B Analyt Technol Biomed Life Sci. 2013;931:90-96.

Villanueva J, Infante J, Krepler C, Reyes-Uribe P, Samanta M, Chen H-Y, Li B, Swoboda R, Wilson M, Vultur A, Fukunaga-Kalabis M, Wubbenhorst B, Chen TY, Liu Q, Sproesser K, DeMarini D, Gilmer T, Martin A-M, Marmorstein R, Schultz D, Speicher D, Karakousis G, Xu W, Amaravadi R, Xu X, Schuchter L, Herlyn M, Nathanson K. Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Reports. 2013;4:1090-1099.

Basu D, Bewley AF, Sperry SM, Montone KT, Gimotty PA, Rasanen K, Facompre ND, Weinstein GS, Nakagawa H, Diehl JA, Rustgi AK, Herlyn M. EGFR inhibition promotes an aggressive invasion pattern mediated by mesenchymal-like tumor cells within squamous cell carcinomas. Molec Cancer Ther. 2013;12:2176-2186.

Lee EK, Lian Z, D’Andrea K, Letrero R, Sheng W, Liu S, Diehl N, Barbash O, Schuchter LM, Amaravadi RK, Xu X, Herlyn M, Nathanson KL, Diehl JA. The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma. Mol Cell Biol. 2013;33:4422-4433.

Rasänen K, Speicher K, Valiga A, Tang H-Y, Zhang G, Perego M, Somasundaram R, Li L, Sriwasdi S, Klein-Szanto A, Basu D, Rustgi AK, Speicher DW, Herlyn M. Comparative secretome analysis of epithelial and mesenchymal subpopulations of head and neck squamous cell carcinoma identifies S100A4 as a potential therapeutic target. Molec Cell Proteomics. 2013;12(12):3778-92.

Wang T, Ge Y, Xiao M, Lopez-Coral A, Li L, Roesch A, Huang C, Alexander P, Vogt T, Xu X, Hwang W-T, Lieu M, Belser E, Liu R, Somasundaram R, Herlyn M, Kaufman RE. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol. 2013 Oct 24 [Epub ahead of print].

Wong GS, Lee JS, Park YY, Klein-Szanto AJ, Waldron TJ, Cukierman E, Herlyn M,
Gimotty P, Nakagawa H, Rustgi AK. Periostin cooperates with mutant p53 to mediate invasion through the induction of STAT1 signaling in the esophagus tumor microenvironment. Oncogenesis. 2013;2:e59.

O’Connell M, Marchbank K, Webster M, Valiga A, Kaur A, Vultur A, Li L, Herlyn M, Villanueva J, Liu Q, Yin X, Widura S, Nelson J, Ruiz N, Camilli T, Indig FE, Flaherty K, Wargo J, Frederick DT, Cooper Z, Nair S, Amaravadi R, Schuchter L, Karakousis G, Xu W, Xu X, Weeraratna AT. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Disc. 2013;3(12):1378-93.

Wellcome Trust Sanger Institute

Our Group

Experimental Cancer Genetics
Wellcome Trust Sanger Institute

 

Group Leader

Dr. David Adams
Senior Group Leader / CR UK Senior Fellow
Experimental Cancer Genetics
Wellcome Trust Sanger Institute
Hinxton, Cambs, CB10 1HH
Ph:  +44 (0) 1223 834 244
Fax: +44 (0) 1223 494 919

Victoria Russell-Hopkins (PA) vr4@sanger.ac.uk

 

Group Members

Louise van der Weyden          (Senior Staff Scientist)               – CR-UK Funded.
Annie Speak                              (Senior Staff Scientist)               – WT Funded.
Chi Wong                                   (Consultant in Haematology)   – WT Fellowship.
Vivek Iyer                                  (Principal Bioinformatician)     – WT Funded.
James Hewinson                     (Lab Manager)                              – WT Funded.
Marcela Sjoberg                      (Postdoc)                                        – EU Funded.
Nic Walker                               (Postdoc)                                        – EU Funded.
Emmanuelle Supper              (Postdoc)                                        – WT Fellowship.
Marco Ranzani                       (Postdoc)                                         – Marie Curie Funded.
Clara Alsinet-Armengol        (Postdoc)                                        – ERC Funded.
Kim Wong                               (Senior Computer Biologist)      – ERC Funded.
Sendu Bala                              (Senior Computer Biologist)      – EU Funded.
Mamun Rashid                      (Senior Computer Biologist)      – CR-UK funded.
Martin del Castillo                (PhD Student)                               – CR-UK studentship.
Gemma Turner                      (PhD Student)                               – MRC Funded.
Katharina Strege                    (PhD Student)                              – MRC Funded.
Richard Gunning                   (PhD Student)                              – BBSRC Funded.
Stefan Dentro                        (PhD Student)                               – WT Funded.
Nicky Thompson                  (Clinical PhD Student)                – WT Funded.
Sofia Chen                             (PhD Student)                               – EU Funded.
Aravind Sankar                    (PhD Student)                               – EU Funded.
Roy Rabbie                            (Clinical PhD Student)               – NHS/CR-UK Funded.
Daniela Robles                     (Visiting scientist)                       – Mexican Government.
Mairi Kusma                         (animal technician)                    – EU Funded.
Victoria                                  (animal technician)                    – EU Funded.

 

Research

Dr. David Adams and his group study the mechanisms of cancer development, particularly skin cancer (melanoma) and colorectal cancer. They sequence DNA from families with a high incidence of cancer, and also tumours from patients to understand why some people are at greater risk of tumour development and how cancers evolve. The group also performs functional studies in cultured cells and in mice to understand how factors such as DNA mutations and the immune system influence tumour growth.

 

Publications

Josep V. Forment, Mareike Herzog, Julia Coates, Tomasz Konopka, Bianca V. Gapp, Sebastian M. Nijman, Adams DJ, Keane TM,, Jackson SP. Genome-wide genetic screening with chemically-mutagenized haploid embryonic stem cells. Nature Structural and Molecular Biologyin press

Dickinson M., et al., Adams DJ, Lloyd K, McKerlie C, Beaudet AL, Bucan M, Murray SA. High-throughput discovery of novel developmental phenotypes. Nature – in press

McIntyre RE, Nicod J, Robles-Espinoza CD, Maciejowski J, Cai N, Hill J, Verstraten R, Iyer V, Rust AG, Balmus G, Mott R, Flint J, Adams DJ (2016) A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice. G3 in press

Nicod J, Davies RW, Cai N, Hassett C, Goodstadt L, Cosgrove C, Yee BK, Lionikaite V, McIntyre RE, Remme CA, Lodder EM, Gregory JS, Hough T, Joynson R, Phelps H, Nell B, Rowe C, Wood J, Walling A, Bopp N, Bhomra A, Hernandez-Pliego P, Callebert J, Aspden RM, Talbot NP, Robbins PA, Harrison M, Fray M, Launay JM, Pinto YM, Blizard DA, Bezzina CR, Adams DJ, Franken P, Weaver T, Wells S, Brown SD, Potter PK, Klenerman P, Lionikas A, Mott R, Flint J (2016) Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing. Nature genetics in press

van der Weyden L, Patton EE, Wood GA, Foote AK, Brenn T, Arends MJ, Adams DJ (2016) Cross-species models of human melanoma. The Journal of pathology 238: 152-165

Robles-Espinoza CD, Roberts ND, Chen S, Leacy FP, Alexandrov LB, Pornputtapong N, Halaban R, Krauthammer M, Cui R, Timothy Bishop D, Adams DJ (2016) Germline MC1R status influences somatic mutation burden in melanoma. Nature communications 7: 12064

Rabbie R, Adams DJ (2016) Desmoplastic melanoma: C>Ts and NF-kappaB. Pigment Cell Melanoma Res 29: 120-121

Kemper K, Krijgsman O, Kong X, Cornelissen-Steijger P, Shahrabi A, Weeber F, van der Velden DL, Bleijerveld OB, Kuilman T, Kluin RJ, Sun C, Voest EE, Ju YS, Schumacher TN, Altelaar AF, McDermott U, Adams DJ, Blank CU, Haanen JB, Peeper DS (2016) BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts. Cell reports 16: 263-277

Harland M, Petljak M, Robles-Espinoza CD, Ding Z, Gruis NA, van Doorn R, Pooley KA, Dunning AM, Aoude LG, Wadt KA, Gerdes AM, Brown KM, Hayward NK, Newton-Bishop JA, Adams DJ, Bishop DT (2016) Germline TERT promoter mutations are rare in familial melanoma. Fam Cancer 15: 139-144

Robles-Espinoza CD, Velasco-Herrera Mdel C, Hayward NK, Adams DJ (2015) Telomere-regulating genes and the telomere interactome in familial cancers. Mol Cancer Res 13: 211-222

Ranzani M, Alifrangis C, Perna D, Dutton-Regester K, Pritchard A, Wong K, Rashid M, Robles-Espinoza CD, Hayward NK, McDermott U, Garnett M, Adams DJ (2015) BRAF/NRAS wild-type melanoma, NF1 status and sensitivity to trametinib. Pigment Cell Melanoma Res 28: 117-119

Perna D, Karreth FA, Rust AG, Perez-Mancera PA, Rashid M, Iorio F, Alifrangis C, Arends MJ, Bosenberg MW, Bollag G, Tuveson DA, Adams DJ (2015) BRAF inhibitor resistance mediated by the AKT pathway in an oncogenic BRAF mouse melanoma model. Proceedings of the National Academy of Sciences of the United States of America 112: E536-545

McCreery MQ, Halliwill KD, Chin D, Delrosario R, Hirst G, Vuong P, Jen KY, Hewinson J, Adams DJ, Balmain A (2015) Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat Med 21: 1514-1520

Kuilman T, Velds A, Kemper K, Ranzani M, Bombardelli L, Hoogstraat M, Nevedomskaya E, Xu G, de Ruiter J, Lolkema MP, Ylstra B, Jonkers J, Rottenberg S, Wessels LF, Adams DJ, Peeper DS, Krijgsman O (2015) CopywriteR: DNA copy number detection from off-target sequence data. Genome biology 16: 49

Kemper K, Krijgsman O, Cornelissen-Steijger P, Shahrabi A, Weeber F, Song JY, Kuilman T, Vis DJ, Wessels LF, Voest EE, Schumacher TN, Blank CU, Adams DJ, Haanen JB, Peeper DS (2015) Intra- and inter-tumor heterogeneity in a vemurafenib-resistant melanoma patient and derived xenografts. EMBO Mol Med 7: 1104-1118

Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Leopold V, Sjoberg M, Keane TM, Verma A, Ala U, Tay Y, Wu D, Seitzer N, Velasco-Herrera Mdel C, Bothmer A, Fung J, Langellotto F, Rodig SJ, Elemento O, Shipp MA, Adams DJ, Chiarle R, Pandolfi PP (2015) The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 161: 319-332

Aoude LG, Pritchard AL, Robles-Espinoza CD, Wadt K, Harland M, Choi J, Gartside M, Quesada V, Johansson P, Palmer JM, Ramsay AJ, Zhang X, Jones K, Symmons J, Holland EA, Schmid H, Bonazzi V, Woods S, Dutton-Regester K, Stark MS, Snowden H, van Doorn R, Montgomery GW, Martin NG, Keane TM, Lopez-Otin C, Gerdes AM, Olsson H, Ingvar C, Borg A, Gruis NA, Trent JM, Jonsson G, Bishop DT, Mann GJ, Newton-Bishop JA, Brown KM, Adams DJ, Hayward NK (2015) Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma. J Natl Cancer Inst 107

Wong CC, Martincorena I, Rust AG, Rashid M, Alifrangis C, Alexandrov LB, Tiffen JC, Kober C, Green AR, Massie CE, Nangalia J, Lempidaki S, Dohner H, Dohner K, Bray SJ, McDermott U, Papaemmanuil E, Campbell PJ, Adams DJ(2014) Inactivating CUX1 mutations promote tumorigenesis. Nature genetics 46: 33-38

Robles-Espinoza CD, Harland M, Ramsay AJ, Aoude LG, Quesada V, Ding Z, Pooley KA, Pritchard AL, Tiffen JC, Petljak M, Palmer JM, Symmons J, Johansson P, Stark MS, Gartside MG, Snowden H, Montgomery GW, Martin NG, Liu JZ, Choi J, Makowski M, Brown KM, Dunning AM, Keane TM, Lopez-Otin C, Gruis NA, Hayward NK, Bishop DT, Newton-Bishop JA, Adams DJ (2014) POT1 loss-of-function variants predispose to familial melanoma. Nature genetics 46: 478-481

Yen J, White RM, Wedge DC, Van Loo P, de Ridder J, Capper A, Richardson J, Jones D, Raine K, Watson IR, Wu CJ, Cheng J, Martincorena I, Nik-Zainal S, Mudie L, Moreau Y, Marshall J, Ramakrishna M, Tarpey P, Shlien A, Whitmore I, Gamble S, Latimer C, Langdon E, Kaufman C, Dovey M, Taylor A, Menzies A, McLaren S, O’Meara S, Butler A, Teague J, Lister J, Chin L, Campbell P, Adams DJ, Zon LI, Patton EE, Stemple DL, Futreal PA (2013) The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models. Genome biology 14: R113

van der Weyden L, Arends MJ, Rust AG, Poulogiannis G, McIntyre RE, Adams DJ(2012) Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1. Molecular cancer 11: 29

Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP (2011) In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147: 382-395

Wood HM, Belvedere O, Conway C, Daly C, Chalkley R, Bickerdike M, McKinley C, Egan P, Ross L, Hayward B, Morgan J, Davidson L, MacLennan K, Ong TK, Papagiannopoulos K, Cook I, Adams DJ, Taylor GR, Rabbitts P (2010) Using next-generation sequencing for high resolution multiplex analysis of copy number variation from nanogram quantities of DNA from formalin-fixed paraffin-embedded specimens. Nucleic acids research 38: e151

Wong K, Keane TM, Stalker J, Adams DJ (2010) Enhanced structural variant and breakpoint detection using SVMerge by integration of multiple detection methods and local assembly. Genome biology 11: R128

Medical University of Vienna, Austria

Medical University of Vienna
Department of Dermatology
Währinger Gürtel 18-20, 1090 Wien
T: +43 (0)1 40400-0
M3 Study Group
Department of Dermatology
Medical University of Vienna
Währinger Gürtel 18-20
A-1090 Vienna, Austria

Group leader

Ichiro Okamoto
ichiro.okamoto@meduniwien.ac.at
Tel: +43-(0)1-40400-77000

Group members

Judith Wendt
judith.wendt@meduniwien.ac.at
Tel: +43-(0)1-40400-77000

Christoph Müller
christoph.mueller@meduniwien.ac.at
Tel: +43-(0)1-40400-77000

Research area

The M3-study (Molecular Marker in Melanoma) has been established in 2008 to study genetic and phenotypic markers of melanoma risk and progression of current patients. Patients’ recruitment including controls for studies identifying risk factors are ongoing. So far, more than 1800 melanoma patients and more than 1600 controls have participated to this study. Participants with familial melanoma background, multiple primary melanomas and young melanoma patients are of special interest. The following list represents the most recent scientific output by the group:

List of publications

  • Wendt J., Rauscher S., Burgstaller-Muehlbacher S., Fae I., Fischer G., Pehamberger H., Okamoto I. (2016) Human Determinants and the Role of Melanocortin-1-Receptor Variants in Melanoma Risk Independent of UV Radiation Exposure, JAMA Dermatology
  • Davies, J. R., Jewell, R., Affleck, P., Anic, G. M., Randerson-Moor, J., Ozola, A., Egan, K. M., Elliott, F., Garcia-Casado, Z., Hansson, J., Harland, M., Hoiom, V., Jian, G., Jonsson, G., Kumar, R., Nagore, E., Wendt, J., Olsson, H., Park, J. Y., Patel, P., Pjanova, D., Puig, S., Schadendorf, D., Sivaramakrishna Rachakonda, P., Snowden, H., Stratigos, A. J., Bafaloukos, D., Ogbah, Z., Sucker, A., Van den Oord, J. J., Van Doorn, R., Walker, C., Okamoto, I., Wolter, P., Barrett, J. H., Timothy Bishop, D. & Newton-Bishop, J. (2014) Inherited variation in the PARP1 gene and survival from melanoma, Int J Cancer. 135, 1625-33. Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/24535833 International Journal of Cancer: http://onlinelibrary.wiley.com/doi/10.1002/ijc.28796/abstract http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106984/
  • Davies, J. R., Field, S., Randerson-Moor, J., Harland, M., Kumar, R., Anic, G. M., Nagore, E., Hansson, J., Hoiom, V., Jonsson, G., Gruis, N. A., Park, J. Y., Guan, J., Sivaramakrishna Rachakonda, P., Wendt, J., Pjanova, D., Puig, S., Schadendorf, D., Okamoto, I., Olsson, H., Affleck, P., Garcia-Casado, Z., Puig-Butille, J. A., Stratigos, A. J., Kodela, E., Donina, S., Sucker, A., Hosen, I., Egan, K. M., Barrett, J. H., van Doorn, R., Bishop, D. T. & Newton-Bishop, J. (2014) An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study, Pigment Cell Melanoma Res. 27, 234-43. Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/24219834 Pigment Cell & Melanoma Research: http://onlinelibrary.wiley.com/doi/10.1111/pcmr.12193/abstract http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065372/
  • Iles, M. M., Law, M. H., Stacey, S. N., Han, J., Fang, S., Pfeiffer, R., Harland, M., Macgregor, S., Taylor, J. C., Aben, K. K., Akslen, L. A., Avril, M. F., Azizi, E., Bakker, B., Benediktsdottir, K. R., Bergman, W., Scarra, G. B., Brown, K. M., Calista, D., Chaudru, V., Fargnoli, M. C., Cust, A. E., Demenais, F., de Waal, A. C., Debniak, T., Elder, D. E., Friedman, E., Galan, P., Ghiorzo, P., Gillanders, E. M., Goldstein, A. M., Gruis, N. A., Hansson, J., Helsing, P., Hocevar, M., Hoiom, V., Hopper, J. L., Ingvar, C., Janssen, M., Jenkins, M. A., Kanetsky, P. A., Kiemeney, L. A., Lang, J., Lathrop, G. M., Leachman, S., Lee, J. E., Lubinski, J., Mackie, R. M., Mann, G. J., Martin, N. G., Mayordomo, J. I., Molven, A., Mulder, S., Nagore, E., Novakovic, S., Okamoto, I., Olafsson, J. H., Olsson, H., Pehamberger, H., Peris, K., Grasa, M. P., Planelles, D., Puig, S., Puig-Butille, J. A., Randerson-Moor, J., Requena, C., Rivoltini, L., Rodolfo, M., Santinami, M., Sigurgeirsson, B., Snowden, H., Song, F., Sulem, P., Thorisdottir, K., Tuominen, R., Van Belle, P., van der Stoep, N., van Rossum, M. M., Wei, Q., Wendt, J., Zelenika, D., Zhang, M., Landi, M. T., Thorleifsson, G., Bishop, D. T., Amos, C. I., Hayward, N. K., Stefansson, K., Bishop, J. A. & Barrett, J. H. (2013) A variant in FTO shows association with melanoma risk not due to BMI, Nat Genet. 45, 428-32. Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/23455637 Nature genetics: http://www.nature.com/ng/journal/v45/n4/full/ng.2571.html http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640814/
  • Davies, J. R., Field, S., Randerson-Moor, J., Harland, M., Kumar, R., Anic, G. M., Nagore, E., Hansson, J., Hoiom, V., Jonsson, G., Gruis, N. A., Park, J. Y., Jian, G., Rachakonda, P. S., Wendt, J., Pjanova, D., Puig, S., Schadendorf, D., Okamoto, I., Olsson, H., Affleck, P., Garcia-Casado, Z., Puig-Butille, J. A., Stratigos, A. J., Kodela, E., Donina, S., Sucker, A., Hosen, I., Egan, K. M., Barrett, J. H., van Doorn, R., Bishop, D. T. & Newton-Bishop, J. (2013) An inherited variant in the gene coding for vitamin D binding protein and survival from cutaneous melanoma: a BioGenoMEL study, Pigment Cell Melanoma Res. Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/24219834 Pigment Cell & Melanoma Research: http://onlinelibrary.wiley.com/doi/10.1111/pcmr.12193/abstract http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065372/
  • Stacey, S. N., Sulem, P., Masson, G., Gudjonsson, S. A., Thorleifsson, G., Jakobsdottir, M., Sigurdsson, A., Gudbjartsson, D. F., Sigurgeirsson, B., Benediktsdottir, K. R., Thorisdottir, K., Ragnarsson, R., Scherer, D., Hemminki, K., Rudnai, P., Gurzau, E., Koppova, K., Botella-Estrada, R., Soriano, V., Juberias, P., Saez, B., Gilaberte, Y., Fuentelsaz, V., Corredera, C., Grasa, M., Hoiom, V., Lindblom, A., Bonenkamp, J. J., van Rossum, M. M., Aben, K. K., de Vries, E., Santinami, M., Di Mauro, M. G., Maurichi, A., Wendt, J., Hochleitner, P., Pehamberger, H., Gudmundsson, J., Magnusdottir, D. N., Gretarsdottir, S., Holm, H., Steinthorsdottir, V., Frigge, M. L., Blondal, T., Saemundsdottir, J., Bjarnason, H., Kristjansson, K., Bjornsdottir, G., Okamoto, I., Rivoltini, L., Rodolfo, M., Kiemeney, L. A., Hansson, J., Nagore, E., Mayordomo, J. I., Kumar, R., Karagas, M. R., Nelson, H. H., Gulcher, J. R., Rafnar, T., Thorsteinsdottir, U., Olafsson, J. H., Kong, A. & Stefansson, K. (2009) New common variants affecting susceptibility to basal cell carcinoma, Nat Genet. 41, 909-14. Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/19578363 Nature genetics: http://www.nature.com/ng/journal/v41/n8/full/ng.412.html http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973331/