Instituto Valenciano de Oncologia

Instituto Valenciano de Oncología
Department of Dermatology, c/ Professor Beltrán Báguena, 8; 46009 Valencia, Spain

T: +34961114015

Website
www.ivo.es/homes/index/language:eng

Group Leader

Professor Eduardo Nagore, M.D., Ph.D.
Section Chief
Department of Dermatology
eduardo_nagore@ono.com

Group Members

Professor Rajiv Kumar (r.kumar@dkfz-heidelberg.de) – German Cancer Research Center in Heidelberg, Germany.
Dr Zaida García-Casado (zaida.garcia18@gmail.com) – Senior Scientific Officer
Dr Celia Requena (celiareq@hotmail.com) – Senior Scientific Officer
Arantxa Rodríguez (arantxaroher@gmail.com) – Research Nurse

Research

The group is established in the city of Valencia, the capital of the region of Valencia, Spain. The region is in the Eastern coast of Spain. The group includes Prof. Rajiv Kumar’s group from Heidelberg, Germany, who leads the study of low penetrance genes in the cohort.

The center is an oncology hospital which takes referrals for genetic testing of melanoma from the region, with a catchment population of 5 million inhabitants.

Routine analyses of CDKN2A, CDK4, MITF and MC1R is performed for families fulfilling the criteria for familial melanoma in a low melanoma incident region.

Melanoma Research

In the melanoma group, lead by Professor Eduardo Nagore, we have the following research areas:

  • Study of high penetrance genes in familial melanoma and patients with multiple primary melanomas (in collaboration with NCI/NIH, Dr. Maria Teresa Landi). We have a series of 160 families.
  • Study of low/intermediate penetrance genes in sporadic melanomas (in collaboration with Prof Rajiv Kumar): we have a cohort of 2000 cases with full information about phenotype and environmental factors.
  • Study of prognostic factors for survival, including germline (BioGenoMEL group) and somatic genetic alterations (in collaboration with Prof Rajiv Kumar). The cohort data include full information about survival, updated in a daily basis and confirmed by checking the National Mortality Registry.
  • Study of Spitzoid tumors (lead by Dr Requena).
  • Identification of second malignancies in melanoma survivors.
  • Study of low/intermediate penetrance genes in sporadic melanomas (in collaboration with NCI/NIH, Dr. Maria Teresa Landim and Prof Rajiv Kumar): we have a cohort of approximately 2000 cases with full information about phenotype and environmental factors.

Information for families from Spain

The center offers facilities for the study of families from other regions of Spain, either by genetic testing or genetic counselling.

Publications

Related to melanoma predisposition:

1: Nagore E, Reyes-Garcia D, Heidenreich B, Garcia-Casado Z, Requena C, Kumar R.TERT promoter mutations associate with MC1R variants in melanoma patients.Pigment Cell Melanoma Res. 2016 Dec 8. doi: 10.1111/pcmr.12567. [Epub ahead of print] PubMed PMID: 27930874.

2: Hernández-Ostiz S, Pérez-Ramada MD, Ortiz B, Requena C, Ribas G, Aznar E,Nagore E. 25-Hydroxyvitamin D in Patients With Melanoma and Factors Associated With Inadequate Levels. Actas Dermosifiliogr. 2016 Nov;107(9):758-764. dos: 10.1016/j.ad.2016.06.002. English, Spanish. PubMed PMID: 27418183.

3: Tagliabue E, Gandini S, García-Borrón JC, Maisonneuve P, Newton-Bishop J, Polsky D, Lazovich D, Kumar R, Ghiorzo P, Ferrucci L, Gruis NA, Puig S, Kanetsky PA, Motokawa T, Ribas G, Landi MT, Fargnoli MC, Wong TH, Stratigos A, Helsing P, Guida G, Autier P, Han J, Little J, Sera F, Raimondi S; M-SKIP Study group. Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled Analysis from the M-Skip Project. J Invest Dermatol. 2016 Sep;136(9):1914-7. doi: 10.1016/j.jid.2016.05.099. PubMed PMID: 27251790.

4: Taylor NJ, Handorf EA, Mitra N, Avril MF, Azizi E, Bergman W, Bianchi-Scarrà G, Bishop DT, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Cuellar F, Cust AE, Demenais F, Elder DE, Friedman E, Gerdes AM, Ghiorzo P, Goldstein AM, Grazziotin TC, Hansson J, Hayward NK, Hocevar M, Höiom V, Holland EA, Ingvar C, Landi MT, Landman G, Larre-Borges A, Leachman SA, Mann GJ, Nagore E, Olsson H, Palmer J, Perić B, Pjanova D, Puig S, Schmid H, van der Stoep N, Tucker MA, Wadt KA, Whitaker L, Yang XR, Newton Bishop JA, Gruis NA, Kanetsky PA; GenoMEL Consortium.. Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of Melanoma Families. J Invest Dermatol. 2016 May;136(5):1066-9. doi: 10.1016/j.jid.2016.01.009. PubMed PMID:
26827760.

5: Espinosa P, Pfeiffer RM, García-Casado Z, Requena C, Landi MT, Kumar R, Nagore Risk factors for keratinocyte skin cancer in patients diagnosed with melanoma,a large retrospective study. Eur J Cancer. 2016 Jan;53:115-24. dos:10.1016/j.ejca.2015.10.058. PubMed PMID: 26702765.

6: 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. 2016 Jul;18(7):727-36. doi: 10.1038/gim.2015.160. PubMed PMID: 26681309; PubMed Central PMCID: PMC4940430.

7: 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, García-Borrón JC, Kanetsky PA, Landi MT, Little J, Newton-Bishop J, Sera F, Raimondi S; M-SKIP Study Group.. MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project. Br J Cancer. 2015 Jul 14;113(2):354-63. doi: 10.1038/bjc.2015.231. PubMed PMID: 26103569; PubMed Central PMCID: PMC4506395.

8: Márquez-Rodas I, Martín González M, Nagore E, Gómez-Fernández C, Avilés-Izquierdo JA, Maldonado-Seral C, Soriano V, Majem-Tarruella M, Palomar V, Maseda R, Martín-Carnicero A, Puertolas T, Godoy E, Cerezuela P, Ochoa de Olza M, Campos B, Perez-Ruiz E, Soria A, Gil-Arnaiz I, Gonzalez-Cao M, Galvez E, Arance A, Belon J, de la Cruz-Merino L, Martín-Algarra S; Spanish Multidisciplinary Group of Melanoma (GEM).. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study. PLoS One. 2015 Apr 13;10(4):e0124239. dos: 10.1371/journal.pone.0124239. PubMed PMID: 25874698; PubMed Central PMCID: PMC4395344.

9: Cust AE, Pickles KM, Goumas C, Vu T, Schmid H, Nagore E, Kelly J, Aitken JF, Giles GG, Hopper JL, Jenkins MA, Mann GJ. Accuracy of self-reported nevus and pigmentation phenotype compared with clinical assessment in a population-based study of young Australian adults. Cancer Epidemiol Biomarkers Prev. 2015 Apr;24(4):736-43. doi: 10.1158/1055-9965.EPI-14-1203. PubMed PMID: 25628333; PubMed Central PMCID: PMC4698346.

10: 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 Jul;54(7):778-84. doi: 10.1111/ijd.12496. PubMed PMID: 25771683.

11: Bertolin M, Cercatto MC, Requena C, Serra-Guillen C, Llombart B, Sanmartin O, Guillen C, Nagore E. Awareness, Attitude, and Adherence to Preventive Measures in Patients at High Risk of Melanoma. A Cross-Sectional Study on 185 Patients. J Cancer Educ. 2015 Sep;30(3):552-66. doi: 10.1007/s13187-014-0766-z. PubMed PMID: 25510366.

12: 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, Soufir N. Genes involved in the WNT and vesicular trafficking pathways are associated with melanoma predisposition. Int J Cancer. 2015 May 1;136(9):2109-19. dos: 10.1002/ijc.29257. PubMed PMID: 25303718.

13: 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 Feb 1;136(3):618-31. doi: 10.1002/ijc.29018. PubMed PMID: 24917043; PubMed Central PMCID: PMC4378685.

14: Arroyo-Berdugo Y, Alonso S, Ribas G, Ibarrola-Villava M, Peña-Chilet M, Martínez-Cadenas C, Gardeazabal J, Ratón-Nieto JA, Sánchez-Díez A, Careaga JM, Pérez-Yarza G, Carretero G, Martín-González M, Gómez-Fernández C, Nagore E, Asumendi A, Boyano MD. Involvement of ANXA5 and ILKAP in susceptibility to malignant melanoma. PLoS One. 2014 Apr 17;9(4):e95522. dos: 10.1371/journal.pone.0095522. PubMed PMID: 24743186; PubMed Central PMCID: PMC3990692.

15: Shi J, Yang XR, Ballew B, Rotunno M, Calista D, Fargnoli MC, Ghiorzo P, Bressac-de Paillerets B, Nagore E, Avril MF, Caporaso NE, McMaster ML, Cullen M, Wang Z, Zhang X; NCI DCEG Cancer Sequencing Working Group.; NCI DCEG Cancer Genomics Research Laboratory.; French Familial Melanoma Study Group., Bruno W, Pastorino L, Queirolo P, Banuls-Roca J, Garcia-Casado Z, Vaysse A, Mohamdi H, Riazalhosseini Y, Foglio M, Jouenne F, Hua X, Hyland PL, Yin J, Vallabhaneni H, Chai W, Minghetti P, Pellegrini C, Ravichandran S, Eggermont A, Lathrop M, Peris K, Scarra GB, Landi G, Savage SA, Sampson JN, He J, Yeager M, Goldin LR, Demenais F, Chanock SJ, Tucker MA, Goldstein AM, Liu Y, Landi MT. Rare missens variants in POT1 predispose to familial cutaneous malignant melanoma. Nat Genet. 2014 May;46(5):482-6. doi: 10.1038/ng.2941. PubMed PMID: 24686846; PubMed Central PMCID: PMC4056593.

16: 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, Sivaramakrishna Rachakonda P, 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, Timothy Bishop D, Newton-Bishop J. Inherited variation in the PARP1 gene and survival from melanoma. Int J Cancer. 2014 Oct 1;135(7):1625-33. doi: 10.1002/ijc.28796. PubMed PMID: 24535833; PubMed Central PMCID: PMC4106984.

17: Echeverría B, Bulliard JL, Guillén C, Nagore E. Indicators for the total number of melanocytic naevi: an adjunct for screening campaigns. Observational study on 292 patients. Br J Dermatol. 2014 Jan;170(1):144-9. dos: 10.1111/bjd.12692. PubMed PMID: 24443914.

18: 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 Mar;105(2):159-71. doi: 10.1016/j.ad.2013.10.001. English, Spanish. PubMed PMID: 24238329.

19: 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, Guan J, Sivaramakrishna Rachakonda P, 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 Mar;27(2):234-43. doi: 10.1111/pcmr.12193. PubMed PMID: 24219834; PubMed Central PMCID: PMC4065372.

20: 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 Jul 2;13:325. doi: 10.1186/1471-2407-13-325. PubMed PMID: 23816148; PubMed Central PMCID: PMC3702420.

21: 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 Oct;169(4):804-11. doi: 10.1111/bjd.12418. PubMed PMID: 23647022; PubMed Central PMCID: PMC3863403.

22: Ríos L, Nagore E, López JL, Redondo P, Martí RM, Fernández-de-Misa R, Soler Melanoma characteristics at diagnosis from the Spanish National Cutaneous Melanoma Registry: 15 years of experience. Actas Dermosifiliogr. 2013 Nov;104(9):789-99. doi: 10.1016/j.ad.2013.02.003. English, Spanish. PubMed PMID: 23622931.

23: Peña-Chilet M, Ibarrola-Villava M, Martin-González M, Feito M, Gomez-Fernandez C, Planelles D, Carretero G, Lluch A, Nagore E, Ribas G.rs12512631 on the group specific complement (vitamin D-binding protein GC) implicated in melanoma susceptibility. PLoS One. 2013;8(3):e59607. doi: 10.1371/journal.pone.0059607. PubMed PMID: 23544077; PubMed Central PMCID: PMC3609832.

24: Iles MM, Law MH, Stacey SN, Han J, Fang S, Pfeiffer R, Harland M, Macgregor S, Taylor JC, Aben KK, Akslen LA, Avril MF, Azizi E, Bakker B, Benediktsdottir KR, Bergman W, Scarrà GB, Brown KM, Calista D, Chaudru V, Fargnoli MC, Cust AE, Demenais F, de Waal AC, Dębniak T, Elder DE, Friedman E, Galan P, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Helsing P, Hočevar M, Höiom V,Hopper JL, Ingvar C, Janssen M, Jenkins MA, Kanetsky PA, Kiemeney LA, Lang J, Lathrop GM, Leachman S, Lee JE, Lubiński J, Mackie RM, Mann GJ, Martin NG, Mayordomo JI, Molven A, Mulder S, Nagore E, Novaković S, Okamoto I, Olafsson JH, Olsson H, Pehamberger H, Peris K, Grasa MP, Planelles D, Puig S, Puig-Butille JA, 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 MM, Wei Q, Wendt J, Zelenika D, Zhang M, Landi MT, Thorleifsson G, Bishop DT, Amos CI, Hayward NK, Stefansson K, Bishop JA, Barrett JH; GenoMEL Consortium.; Q-MEGA and AMFS Investigators.. A variant in FTO shows association with melanoma risk not due to BMI. Nat Genet. 2013 Apr;45(4):428-32, 432e1. doi: 10.1038/ng.2571. PubMed PMID: 23455637; PubMed Central PMCID: PMC3640814.

25: 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 Feb 22;339(6122):959-61. doi:10.1126/science.1230062. PubMed PMID: 23348503.

26: 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. PubMed PMID: 23209811; PubMed Central PMCID: PMC3507747.

27: Hacker E, Nagore E, Cerroni L, Woods SL, Hayward NK, Chapman B, Montgomery GW, Soyer HP, Whiteman DC. NRAS and BRAF mutations in cutaneous melanoma and the association with MC1R genotype: findings from Spanish and Austrian populations. J Invest Dermatol. 2013 Apr;133(4):1027-33. doi: 10.1038/jid.2012.385. PubMed PMID: 23096702.

28: 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. 2013 Jan 1;132(1):42-54. doi: 10.1002/ijc.27648. PubMed PMID: 22628150.

29: Ballester I, Oliver V, Bañuls J, Moragón M, Valcuende F, Botella-Estrada R, Nagore E. Multicenter case-control study of risk factors for cutaneous melanoma in Valencia, Spain. Actas Dermosifiliogr. 2012 Nov;103(9):790-7. doi: 10.1016/j.ad.2012.01.014. English, Spanish. PubMed PMID: 22626452.

30: 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 Aug;22(4):316-9. doi: 10.1097/CMR.0b013e3283541460. PubMed PMID: 22516967.

31: 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 May;25(3):384-94. doi: 10.1111/j.1755-148X.2012.00982.x. PubMed PMID: 22325793; PubMed Central PMCID: PMC3490389.

32: Ibarrola-Villava M, Fernandez LP, Alonso S, Boyano MD, Peña-Chilet M, Pita G, Aviles JA, Mayor M, Gomez-Fernandez C, Casado B, Martin-Gonzalez M, Izagirre N, De la Rua C, Asumendi A, Perez-Yarza G, Arroyo-Berdugo Y, Boldo E, Lozoya R, Torrijos-Aguilar A, Pitarch A, Pitarch G, Sanchez-Motilla JM, Valcuende-Cavero F, Tomas-Cabedo G, Perez-Pastor G, Diaz-Perez JL, Gardeazabal J, Martinez de Lizarduy I, Sanchez-Diez A, Valdes C, Pizarro A, Casado M, Carretero G, Botella-Estrada R, Nagore E, Lazaro P, Lluch A, Benitez J, Martinez-Cadenas C, Ribas G. A customized pigmentation SNP array identifies a novel SNP associated with melanoma predisposition in the SLC45A2 gene. PLoS One. 2011 Apr 29;6(4):e19271. doi: 10.1371/journal.pone.0019271. PubMed PMID: 21559390; PubMed Central PMCID: PMC3084811.

33: Figl A, Scherer D, Nagore E, Bermejo JL, Botella-Estrada R, Gast A, Thirumaran RK, Planelles D, Hemminki K, Schadendorf D, Kumar R. Single-nucleotide polymorphisms in DNA-repair genes and cutaneous melanoma. Mutat Res. 2010 Sep 30;702(1):8-16. doi: 10.1016/j.mrgentox.2010.06.011. PubMed PMID: 20601096.

34: Echeverría B, Botella-Estrada R, Serra-Guillén C, Martorell A, Traves V, Requena C, Sanmartín O, Llombart B, Guillén C, Nagore E. [Increased risk of developing a second primary cutaneous nevus-associated melanoma in patients previously diagnosed with the disease]. Actas Dermosifiliogr. 2010 Oct;101(8):710-6. Spanish. PubMed PMID: 20965014.

35: de Torre C, Garcia-Casado Z, Martínez-Escribano JA, Botella-Estrada R, Bañuls J, Oliver V, Mercader P, Azaña JM, Frias J, Nagore E. Influence of loss of function MC1R variants in genetic susceptibility of familial melanoma in Spain. Melanoma Res. 2010 Aug;20(4):342-8. doi: 10.1097/CMR.0b013e32833b159d. PubMed PMID: 20539244.

36: Garcia-Casado Z, Nagore E, Fernandez-Serra A, Botella-Estrada R, Lopez-Guerrero JA. A germline mutation of p14/ARF in a melanoma kindred. Melanoma Res. 2009 Oct;19(5):335-7. doi: 10.1097/CMR.0b013e32832dd2d4. PubMed PMID: 19741424.

37: Scherer D, Nagore E, Bermejo JL, Figl A, Botella-Estrada R, Thirumaran RK, Angelini S, Hemminki K, Schadendorf D, Kumar R. Melanocortin receptor 1 variants and melanoma risk: a study of 2 European populations. Int J Cancer. 2009 Oct 15;125(8):1868-75. doi: 10.1002/ijc.24548. PubMed PMID: 19585506.

38: Stacey SN, Sulem P, Masson G, Gudjonsson SA, Thorleifsson G, Jakobsdottir M, Sigurdsson A, Gudbjartsson DF, Sigurgeirsson B, Benediktsdottir KR, 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, Höiom V, Lindblom A, Bonenkamp JJ, van Rossum MM, Aben KK, de Vries E, Santinami M, Di Mauro MG, Maurichi A, Wendt J, Hochleitner P, Pehamberger H, Gudmundsson J, Magnusdottir DN, Gretarsdottir S, Holm H, Steinthorsdottir V, Frigge ML, Blondal T, Saemundsdottir J, Bjarnason H, Kristjansson K, Bjornsdottir G, Okamoto I, Rivoltini L, Rodolfo M, Kiemeney LA, Hansson J, Nagore E, Mayordomo JI, Kumar R, Karagas MR, Nelson HH, Gulcher JR, Rafnar T, Thorsteinsdottir U, Olafsson JH, Kong A, Stefansson K. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet. 2009 Aug;41(8):909-14. doi: 10.1038/ng.412. PubMed PMID: 19578363; PubMed Central PMCID: PMC2973331.

39: Nagore E, Montoro A, García-Casado Z, Botella-Estrada R, Insa A, Lluch A, López-Guerrero JA, Guillén C. Germline mutations in CDKN2A are infrequent in female patients with melanoma and breast cancer. Melanoma Res. 2009 Aug;19(4):211-4. doi: 10.1097/CMR.0b013e3283281057. PubMed PMID: 19571771.

40: Nagore E, Hueso L, Botella-Estrada R, Alfaro-Rubio A, Serna I, Guallar J, González I, Ribes I, Guillen C. Smoking, sun exposure, number of nevi and previous neoplasias are risk factors for melanoma in older patients (60 years and over). J Eur Acad Dermatol Venereol. 2010 Jan;24(1):50-7. doi:10.1111/j.1468-3083.2009.03353.x. PubMed PMID: 19563496.

41: Nagore E, Botella-Estrada R, Requena C, Serra-Guillén C, Martorell A, Hueso L, Llombart B, Sanmartín O, Guillén C. [Clinical and epidemiologic profile of melanoma patients according to sun exposure of the tumor site]. Acts Dermosifiliogr. 2009 Apr;100(3):205-11. Spanish. PubMed PMID: 19457306.

42: Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blöndal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ, Einarsson GV, Benediktsdottir KR, Agnarsson BA, Olafsson K, Salvarsdottir A, Bjarnason H, Asgeirsdottir M, Kristinsson KT, Matthiasdottir S, Sveinsdottir SG, Polidoro S, Höiom V, Botella-Estrada R, Hemminki K, Rudnai P, Bishop DT, Campagna M, Kellen E, Zeegers MP, de Verdier P, Ferrer A, Isla D, Vidal MJ, Andres R, Saez B, Juberias P, Banzo J, Navarrete S, Tres A, Kan D, Lindblom A, Gurzau E, Koppova K, de Vegt F, Schalken JA, van der Heijden HF, Smit HJ, Termeer RA, Oosterwijk E, van Hooij O,Nagore E, Porru S, Steineck G, Hansson J, Buntinx F, Catalona WJ, Matullo G, Vineis P, Kiltie AE, Mayordomo JI, Kumar R, Kiemeney LA, Frigge ML, Jonsson T, Saemundsson H, Barkardottir RB, Jonsson E, Jonsson S, Olafsson JH, Gulcher JR, Masson G, Gudbjartsson DF, Kong A, Thorsteinsdottir U, Stefansson K. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009 Feb;41(2):221-7. doi: 10.1038/ng.296. PubMed PMID: 19151717; PubMed Central PMCID: PMC4525478.

43: Figl A, Scherer D, Nagore E, Bermejo JL, Dickes E, Thirumaran RK, Gast A,Hemminki K, Kumar R, Schadendorf D. Single nucleotide polymorphisms in DNA repair genes XRCC1 and APEX1 in progression and survival of primary cutaneous melanoma patients. Mutat Res. 2009 Feb 10;661(1-2):78-84. doi: 10.1016/j.mrfmmm.2008.11.011. PubMed PMID: 19073198.

44: Stacey SN, Gudbjartsson DF, Sulem P, Bergthorsson JT, Kumar R, Thorleifsson G, Sigurdsson A, Jakobsdottir M, Sigurgeirsson B, Benediktsdottir KR. Thorisdottir K, Ragnarsson R, Scherer D, Rudnai P, Gurzau E, Koppova K, Höiom V, Botella-Estrada R, Soriano V, Juberías P, Grasa M, Carapeto FJ, Tabuenca P, Gilaberte Y, Gudmundsson J, Thorlacius S, Helgason A, Thorlacius T, Jonasdottir A, Blondal T, Gudjonsson SA, Jonsson GF, Saemundsdottir J, Kristjansson K, Bjornsdottir G, Sveinsdottir SG, Mouy M, Geller F, Nagore E, Mayordomo JI, Hansson J, Rafnar T, Kong A, Olafsson JH, Thorsteinsdottir U, Stefansson K. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nat Genet. 2008 Nov;40(11):1313-8. doi: 10.1038/ng.234. PubMed PMID: 18849993.

45: Nagore E, Pereda C, Botella-Estrada R, Requena C, Guillén C. Acral lentiginous melanoma presents distinct clinical profile with high cancer susceptibility. Cancer Causes Control. 2009 Feb;20(1):115-9. doi: 10.1007/s10552-008-9221-y. PubMed PMID: 18758972.

46: Gudbjartsson DF, Sulem P, Stacey SN, Goldstein AM, Rafnar T, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Sveinsdottir SG, Magnusson V, Lindblom A, Kostulas K, Botella-Estrada R, Soriano V, Juberías P, Grasa M, Saez B, Andres R, Scherer D, Rudnai P, Gurzau E, Koppova K, Kiemeney LA, Jakobsdottir M, Steinberg S, Helgason A, Gretarsdottir S, Tucker MA, Mayordomo JI, Nagore E, Kumar R, Hansson J, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet. 2008 Jul;40(7):886-91. doi: 10.1038/ng.161. Erratum in: Nat Genet. 2008 Aug;40(8):1029. PubMed PMID:18488027.

47: Nagore E, Botella-Estrada R, Garcia-Casado Z, Requena C, Serra-Guillen C, Llombart B, Sanmartin O, Guillen C. Comparison between familial and sporadic cutaneous melanoma in Valencia, Spain. J Eur Acad Dermatol Venereol. 2008 Aug;22(8):931-6. doi: 10.1111/j.1468-3083.2008.02682.x. PubMed PMID: 18355200.

48: Nagore E, Oliver V, Botella-Estrada R, Moreno-Picot S, Guillén C, Fortea JM. Clinicopathological analysis of 1571 cutaneous malignant melanomas in Valencia, Spain: factors related to tumour thickness. Acta Derm Venereol. 2006;86(1):50-6. PubMed PMID: 16585990.

49: Planelles D, Nagore E, Moret A, Botella-Estrada R, Vila E, Guillén C, Montero HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor. Br J Dermatol. 2006 Feb;154(2):261-6. PubMed PMID: 16433795.

50: Nagore E, Montoro A, Oltra S, Ledesma E, Botella-Estrada R, Millán JM, Oliver V, Fortea JM, Guillén C. Age does not appear to be a major indicator of CDKN2A or CDK4 mutations in melanoma patients in Spain. Melanoma Res. 2005 Dec;15(6):555-8. PubMed PMID: 16314743.

51: Nagore E, Planelles MD, Ledesma E, Millán JM, Insa A, Oliver V, Guillén C, Fortea JM. Molecular genetic analysis of HLA-DR and -DQ alleles in Spanish patients with melanoma. Acta Derm Venereol. 2002;82(2):90-3. PubMed PMID: 12125959.

52: Nagore E, Climent J, Planelles MD, Ledesma E, Rubio-Moscardó F, Fortea JM, Oliver V. Analysis of the CDKN2A and CDK4 genes and HLA-DR and HLA-DQ alleles in two Spanish familial melanoma kindreds. Acta Derm Venereol. 2000 Nov-Dec;80(6):440-2. PubMed PMID: 11243640.

Hospital Clinic Barcelona, IDIBAPS

barcelonapictxt


Our institution

Hospital Clinic Barcelona
IDIBAPS
Villarroel 170
08036 Barcelona
Spain


Our group

Department of Dermatology
(Clinic)
Melanoma Unit
Hospital Clinic Barcelona, IDIBAPS
Villarroel 170
08036 Barcelona
Spain

Genetics Service (Laboratory)
Hospital Clinic Barcelona, IDIBAPS
Villarroel 170
08036 Barcelona
Spain


The name, address and contact e-mail, tel of the group leader

Dr. Susana Puig, MD. PhD
Department of Dermatology
Hospital Clinic Barcelona, IDIBAPS
Villarroel 170
08036 Barcelona
Spain

E-mail: spuig@clinic.ub.es
Phone: +34 93 227 54 00 ext 2422
Fax: +34 93 227 54 38


The Melanoma Unit research program of the Dept. of Dermatology includes three main lines of research: 1. Genetic susceptibility to malignant melanoma and nevogenicity. Somatic genetics of melanoma and nevus development; 2. Immunotherapy and new therapies for melanoma 3. Dermoscopy, new diagnosis and prognosis techniques.

1. The melanoma group has focused particularly on the genetic aspects of the Familial Atypical Multiple Mole-Melanoma syndrome. FAMMM is an excellent example of a multi-factorial disorder in which gene-gene and gene-environment interactions play a crucial role. Our studies on a large collection of families with the FAMMM syndrome have demonstrated that 20% of the families had a mutation in the cell cycle regulator gene CDKN2A. 18% of patients with multiple primary melanomas in our setting are also carriers of CDKN2A mutations. In contrast, the incidence of mutations in sporadic melanomas is very low (1-2%). We have furthermore evaluated variants of the melanocortin 1 receptor (MC1R) gene as a modifier of melanoma risk. In addition, the role of UV light, DNA repair capacity, type of skin and degree of pigmentation in relation to melanoma risk is being investigated. Other genodermatosis and multifactorial cutaneous diseases are also investigated.

2. Our research in melanoma therapy is mainly focused on investigating new therapeutic strategies such as whole attenuated cell vaccines or autologous dendritic cell vaccines. Immunological assays are being performed to investigate host response to these vaccines and clinical trials are being developed to evaluate clinical responses. Furthermore, several therapeutic protocols of chemotherapy, biochemotherapy and/or radiotherapy are being conducted to investigate new treatment strategies.

3. Dermoscopy is a non-invasive technique focused on the diagnosis of pigmented tumors. The accuracy of melanoma diagnosis improves with the use of this technique. Special surveillance programs including total body photography and digital dermoscopy follow-up are being developed for the early diagnosis of melanoma in melanoma kindreds and in individuals with high risk to develop melanoma. Exhaustive analysis of false-negative and false-positive melanomas (by naked eye and dermoscopy), morphological description of non-melanocytic cutaneous tumors and the application of dermoscopy in non-tumoral diseases are also being investigated.

Melanoma research

In the melanoma group, lead by Professor Newton Bishop, we have studied high penetrance genes from families with multiple cases of melanoma. To investigate lower penetrance genes and the interaction between genes and the environment, we are currently recruiting a large cohort of melanoma patients, their families and matched population controls. We have also been studying patients who have relapsed with melanoma and will compare them to controls who have not relapsed in order to look at factors associated with prognosis.


Related Links

Institut de Recerca Biomèdica August Pi i Suñer (IDIBAPS)
www.idibaps.ub.edu/

Hospital Clínic de Barcelona
www.hospitalclinic.org


The names and e-mail addresses of the group members

Principal researchers

Susana Puig, MD. PhD
spuig@clinic.ub.es

Josep Malvehy, MD
jmalvehy@clinic.ub.es

Genetics service

Montserrat Mila
mmila@clinic.ub.es

Celia Badenas
cbadenas@clinic.ub.es

PhD-students

Paula Aguilera

Cristina Carrera

Francisco Cuellar (Latin America coordinator)

Zighe Ogbah

Joan-Anton Puig-Butille

Pedro Zaballos

Technicians

Remedios Cervera

Research nurse / Data Managers

Pablo Iglesias

Dani Gabriel

Psychologist/Genetic Counselling

Melinda Gonzlez


Publications

A Ruiz, S Puig, J Malvehy, C Lazaro, M Lynch, A.M. Gimenez-Arnau, Ll Puig, J Sanchez-Conejo, X Estivill, T Castel.

“CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia”

J Med Genet 36; 490-494 (1999)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10874641

Ruiz A, Nadal M, Puig S, Estivill X.
“Cloning of the human phospholipase A2 activating protein (hPLAP) gene on the chromosome 9p21 melanoma deleted region”
Gene 239: 155-161 (1999)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1057104

S Puig, J Castro, PJ Ventura, C Ascaso, J Malvehy, X Estivill, A Vilalta, M Lecha, T Castel.
“Large deletions of chromosome 9p in cutaneous malignant melanoma identify patients with a high risk of developing metastases”
Melanoma Research; 10: 231-236 (2000)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1089037

Moral A, Lafuente MJ, Lafuente A, Castel T, Balesta AM, Lecha M; Trias M, The MMM Group.
The Use Erytrocyte Glutathione as a predictive marker for malignant melanoma.
Anticancer Research 20: 4757-4760 (2000)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11205213

Rizos H*, Puig S*, Badenas C, Malvehy J, Darmanian AP, Jiménez L, Milà M, Kefford RF.
A melanoma-associated germline mutation in exon 1ß inactivates p14ARF.
Oncogene 20: 5543-7 (2001)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11571653

C Ferrandiz, Bordas X, García-Patos V, Puig S, Pujol R, Smandia A.
Prevalence of Psoriasis in Spain.
EJAD 15: 20-23 (2001)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11451315

E Serra, E Ars, A Ravella, A Sanchez, S Puig, T Rosenbaum, X Estivill, C Lazaro.
Somatic NF1 mutational spectrum in benign neurofibromas: mRNA splice defects are common among point mutations.
Human Genet 108: 416-429 (2001)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11409870

Asumalahti K, Veal C, Laitinen T, Suomela S, Allen M, Elomaa O, Moser M, de Cid R, Ripatti S, Vorechovsky I, Marcusson JA, Nakagawa H, Lazaro C, Estivill X, Capon F, Novelli G, The psoriasis consortium, et al.
Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus.
Hum Mol Genet 2002; 11: 589-597.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11875053

Kefford R, Bishop JN, Tucker M, Bressac-de Paillerets B, Bianchi-Scarra G, Bergman W, Goldstein A, Puig S, Mackie R, Elder D, Hansson J, Hayward N, Hogg D, Olsson H.
Genetic testing for melanoma.
Lancet Oncol (2002) 3:653-654

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12424065

Malvehy J, Puig S.
“Follow up of melanocytic skin lesions with digital dermoscopy”.
Clin Dermatol (2002) 20:297-304

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12074871

Vidal-Sicart S, Pons F, Puig S, Ortega M, Vilalta A, Martín F, Rull R, Palou J, Castel T.
Identification of the sentinel lymph node in patients with malignant melanoma: what are the reasons for mistakes?
Eur J Nucl Med Mol Imaging 2003; 30(3):362-6

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12634963

Vilella R, Benitez D, Mila J, Vilalta A, Rull R, Cuellar F, Conill C, Vidal-Sicart S, Costa J, Yachi E, Palou J, Malvehy J, Puig S, Martí R, Mellado B, Castel T.
Treatment of patients with progressive unresectable metastatic melanoma with a heterologous polyvalent melanoma whole cell vaccine.
Int J Cancer 2003 Sep 10; 106(4):626-31.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12845663

Argenziano G, Soyer HP, Chimenti S, Malvehy J, Puig S et al.
Dermoscopy of pigmented skin lesions. Results of a Consensus Meeting via Internet.
J Am Acad Dermatol (2003) 48: 679-93

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12734496

Yakobson E, Eisenberg S, Isacson R, Halle D, Levy-Lahad E, Catane R, Safro M, Sobolev V, Huot T, Peters G, Ruiz A, Malvehy J, Puig S, Chompret A, Avril MF, Shafir R, Peretz H, Paillerets BB. Eur J
A single Mediterranean, possibly Jewish, origin for the Val59Gly CDKN2A mutation in four melanoma-prone families.
Hum Genet. 2003 Apr;11(4):288

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12700603

Zalaudek I, Argenziano G, Ferrara G, Soyer HP, Corona R, Sera F, Cerroni L, Carbone A, Chiominto A, Cicale L, De Rosa G, Ferrari A, Hoffmann-Wellenhof R, Malvehy J, Peris K, Pizzichetta MA, Puig S, Scaqlvenzi M, Staibano S and Ruocco V.
Clinically equivocal melanocytic skin lesions with features of regression: a dermoscopic-pathologycal study.
Br J Dermatol (2004) 150: 64-71

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14746618

Malvehy J, Puig S.
Dermoscopic Patterns of benign volar melanocytic lesions in patients with atypical mole syndrome.
Arch Dermatol (2004) 140: 538-44

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15148097

Conill C, González-Cao M, Jorcano S, Puig S, Malvehy J, Martí R and Castel T.
Temozolomide as profilaxis of melanoma brain metastases.
Mel Res 2004: 14; 73-4

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15091198

R. Vilella, D. Benítez, J. Milà, M. Lozano, R. Vilana, J. Pomes, X. Tomas, J. Costa, A. Vilalta, J. Malvehy, S. Puig, B. Mellado, R. Martí and T. Castel.
Pilot study of treatment of biochemotherapy-refractory stage IV melanoma patients with autologous dendritic cells pulsed with a heterologous melanoma cell line lysate.
Cancer immunology immunotherapy 2004; 53: 651-8

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14999431

Zalaudek I, Argenziano G, Leinweber B, Luigi Citarella,3 MD; Rainer Hofmann-Wellenhof,1 MD; Josep Malvehy,4 MD; Susana Puig,4 MD; Maria Antonietta Pizzichetta,5 MD; Luc Thomas,6 MD; H. Peter Soyer,1 MD; H. Kerl,1 MD
Dermoscopy OF Bowen´s disease.
Br J Dermatol 2004; 150: 64-71

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15214896

Gonzalez Cao M, Puig S, Mellado B.
Survivin expression in sentinel lymp nodes from melanoma patients.
J Clin Oncol 2004; 22: 2751-2

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15226347

Vidal-Sicart S, Pons F, Fuertes S, Vilalta A, Rull R, Puig S, Palou J, Ortega M, Castel T.
Is the identification of in transit sentinel lymph nodes in malignant melanoma patients really necessary?
Eur J Nucl Med Mol Imaging 2004; 31: 945-9

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14997348

Best 5 publications: 1, 3, 5, 12, 16.

LUMC Dermatology

Group Leader

Dr. Nelleke A. Gruis, Phd

gruis@lumc.nl
https://www.lumc.nl/research/programmes/a-g/80115052947221/

Department of dermatology – skin research laboratory
LUMC, P.O. Box 9600
Room C3-76, C3-S
2300 RC, Leiden
The Netherlands

Group members

Dr R van Doorn-dermatologist
Prof dr W Bergman-dermatologist
Dr N.A. Kukutsch-dermatologist
Dr. M Visser- postdoc
Drs. E Christodoulou- PhD student
Drs. C. Salgado- PhD student

Research

Genetics of melanoma predisposition

The melanoma research group has a longstanding interest in the genetic aspects of familial melanoma, also known as familial atypical multiple mole-melanoma syndrome (FAMMM). Familial melanoma is an example of a disorder in which gene-environment interactions play a crucial role in addition to heritable genetic alterations. Studies on a large collection of families with multiple melanoma cases in The Netherlands demonstrated that 25% of them had a founder mutation in the CDKN2A gene (p16-Leiden mutation). This tumor suppressor gene encodes for the p16 and p14 proteins that are primarily involved in cell cycle regulation. The highly variable risk for p16-Leiden mutation carriers to develop melanoma suggests a role for other genetic and environmental factors. These are the subject of current research, which is mostly performed through participation in the international melanoma genetics consortium GenoMEL (www.genomel.org).

In our search to identify melanoma-predisposing genetic variants we also focused on large sporadic melanoma case-control cohorts. SNP-based genome wide approaches have identified genomic loci that are primarily related to genes in pigmentation pathways. Currently our main focus is to discover novel high penetrance melanoma susceptibility genes through application of whole exome and genome sequencing (WES and WGS). For several novel candidates functional studies have been started.

MC1R & oxidative stress management

We have furthermore evaluated a modifying factor of melanoma risk. Variants of the melanocortin 1 receptor (MC1R) gene are associated with red hair, fair skin and increased risk of melanoma in humans. A typical fair skin type variant turns out to be over-represented in sporadic and familial melanoma patients and is associated with an increased melanoma risk independent of skin type. These findings suggest that MC1R variants are involved in melanoma tumorigenesis in a dual manner; as determinant of fair skin and in a pigmentation signalling-independent pathway. In this regard, the role of UV light and oxidative stress, in relation to type and degree of pigmentation and melanoma risk is investigated.

Epigenetics of melanoma

The identification and functional assessment of epigenetic alterations in melanoma is another research line pursued in our reseach group. Epigenetic alterations, in particular aberrant DNA methylation, have been recognized as important contributors to the malignant phenotype of melanoma cells. Dozens of tumor suppressor genes have been reported to be affected by promoter hypermethylation in melanoma including CDKN2A, PTEN, APAF1, E-cadherin and RASSF1A. Our research lab has been among the first to demonstrate promoter hypermethylation in melanoma and we investigate the contribution of this mechanism to its malignant progression and prognosis.

Melanoma skin model

The research laboratory has extensive experience in developing and studying human skin equivalent models, which are engineered by introducing fibroblasts into a dermal matrix onto which keratinocytes are seeded. The engineered skin models generated at our research laboratory are among the most advanced in their resemblance to native skin. Tissue engineered models of cutaneous melanoma and its precursors are used to study the growth and invasive behavior of melanoma cells in their proper microenvironment. In addition to in vitro melanoma models, organotypic skin cultures containing melanocytes are generated to investigate melanocyte biology.

Clinical Research

The department has the largest pigmented lesion clinic in The Netherlands and serves as a tertiary referral center for (familial) melanoma. The well-organized management of patients with dysplastic naevi and melanoma ensures the availability of clinically annotated patient material for research purposes and the possibility for clinical ‘translation’ of research findings. The special position of our clinic as a melanoma center in The Netherlands is related to a large population of patients with familial melanoma carrying the p16-Leiden mutation living in the vicinity of Leiden. Optimizing the management of patients predisposed to the development of melanoma is one of the goals of our research group. To this end epidemiological studies of genetic and environmental influences on melanoma risk are performed and application of imaging devices in the early diagnosis of melanoma is studied by clinical researchers attached to our department.

 

Publications

1: 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. Germline TERT promoter mutations are rare in familial melanoma. Fam Cancer. 2016 Jan;15(1):139-44. doe: 10.1007/s10689-015-9841-9. PubMed PMID: 26433962; PubMed Central PMCID:PMC4698275.

2: 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 Sep;47(9):987-95. doi: 10.1038/ng.3373. PubMed PMID: 26237428; PubMed Central PMCID: PMC4557485.

3: Gao L, van den Hurk K, Nsengimana J, Laye JP, van den Oord JJ, Beck S, Gruis NA, Zoutman WH, van Engeland M, Newton-Bishop JA, Winnepenninckx VJ, van Doorn R. Prognostic Significance of Promoter Hypermethylation and Diminished Gene Expression of SYNPO2 in Melanoma. J Invest Dermatol. 2015 Sep;135(9):2328-31. doi: 10.1038/jid.2015.163. PubMed PMID: 25918983.

4: Taylor NJ, Handorf EA, Mitra N, Avril MF, Azizi E, Bergman W, Bianchi-Scarrà G, Bishop DT, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Cuellar F, Cust AE, Demenais F, Elder DE, Friedman E, Gerdes AM, Ghiorzo P, Goldstein AM, Grazziotin TC, Hansson J, Hayward NK, Hocevar M, Höiom V, Holland EA, Ingvar C, Landi MT, Landman G, Larre-Borges A, Leachman SA, Mann GJ, Nagore E, Olsson H, Palmer J, Perić B, Pjanova D, Puig S, Schmid H, van der Stoep N, Tucker MA, Wadt KA, Whitaker L, Yang XR, Newton Bishop JA, Gruis NA, Kanetsky PA; GenoMEL Consortium.. Phenotypic and Histopathological Tumor Characteristics According to CDKN2A Mutation Status among Affected Members of Melanoma Families. J Invest Dermatol. 2016 May;136(5):1066-9. doi: 10.1016/j.jid.2016.01.009. PubMed PMID:26827760.

5: Gao L, van den Hurk K, Moerkerk PT, Goeman JJ, Beck S, Gruis NA, van den Oord JJ, Winnepenninckx VJ, van Engeland M, van Doorn R. Promoter CpG island hypermethylation in dysplastic nevus and melanoma: CLDN11 as an epigenetic biomarker for malignancy. J Invest Dermatol. 2014 Dec;134(12):2957-66. dos: 10.1038/jid.2014.270. PubMed PMID: 24999589.

6: Commandeur S, Sparks SJ, Chan HL, Gao L, Out JJ, Gruis NA, van Doorn R, El Ghalbzouri A. In-vitro melanoma models: invasive growth is determined by dermal matrix and basement membrane. Melanoma Res. 2014 Aug;24(4):305-14. dos: 10.1097/CMR.0000000000000079. PubMed PMID: 24892959.

7: van der Rhee JI, Boonk SE, Putter H, Cannegieter SC, Flinterman LE, Hes FJ, de Snoo FA, Mooi WJ, Gruis NA, Vasen HF, Kukutsch NA, Bergman W. Surveillance of second-degree relatives from melanoma families with a CDKN2A germline mutation. Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1771-7. dos: 10.1158/1055-9965.EPI-13-0130. PubMed PMID: 23897584.

8: Gao L, Smit MA, van den Oord JJ, Goeman JJ, Verdegaal EM, van der Burg SH,Stas M, Beck S, Gruis NA, Tensen CP, Willemze R, Peeper DS, van Doorn R. Genome-wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma. Pigment Cell Melanoma Res. 2013 Jul;26(4):542-54. doi: 10.1111/pcmr.12096. PubMed PMID: 23590314.

9: Gao L, van Nieuwpoort FA, Out-Luiting JJ, Hensbergen PJ, de Snoo FA, Bergman W, van Doorn R, Gruis NA. Genome-wide analysis of gene and protein expression of dysplastic naevus cells. J Skin Cancer. 2012;2012:981308. dos:10.1155/2012/981308. PubMed PMID: 23251804; PubMed Central PMCID: PMC3515917.

10: Quint KD, van der Rhee JI, Gruis NA, Ter Huurne JA, Wolterbeek R, van der Stoep N, Bergman W, Kukutsch NA. Melanocortin 1 receptor (MC1R) variants in high melanoma risk patients are associated with specific dermoscopic ABCD features. Acta Derm Venereol. 2012 Nov;92(6):587-92. doi: 10.2340/00015555-1457. PubMed PMID: 22965007.

11: Gruis NA, van Doorn R. Melanocortin 1 receptor function: shifting gears from determining skin and nevus phenotype to fetal growth. J Invest Dermatol. 2012 Aug;132(8):1953-5. doi: 10.1038/jid.2012.216. PubMed PMID: 22797298.

LUMC Clinical Genetics

Our institution

Leiden University Medical Center
Albinusdreef 2
2333 ZA Leiden
The Netherlands


Our group

Department of Clinical Genetics
Leiden University Medical Center
Postbus 9600
2300 RC Leiden
The Netherlands

Department of Clinical Genetics
(Laboratory)
DGA
LUMC building 2
Post zone S-06-P
PO box 9600
2300 RC Leiden


The name, address and contact e-mail, tel of the group leader

Prof. Dr. M. H. Breuning
Department of Clinical Genetics
Leiden University Medical Center
Postbus 9600
2300 RC Leiden
The Netherlands

E-mail: m.h.breuning@lumc.nl
Phone: 071-5266090 / 5266060
Fax: 071-526 6749


Our knowledge of mankind’s hereditary characteristics is growing at a tremendous pace. As a result we are becoming more and more successful at tracking down the causes of congenital defects and hereditary diseases.

The Department of Clinical Genetics at the Leiden University Medical Center (LUMC) strives to apply all of this new knowledge as quickly and well as possible in medical practice. Through close collaboration with the Department of Human Genetics at the Center for Human and Clinical Genetics (CHCG) we are able to speedily put into practice the very latest developments in the diagnosis of hereditary diseases.


Related Links

Clinical Genetics, LUMC
www.lumc.nl/4080/default_english.html

Leiden University Medical Center (LUMC)
www.lumc.nl/english/start_english.html

The Netherlands Foundation for the Detection of Hereditary Tumours
www.stoet.nl


The names and e-mail addresses of group members with a description of their contribution

Management Team Department

Mrs. Dr. C.J. van Asperen
Head Genetic Counseling Section
c.j.van_asperen@lumc.nl

Prof. Dr. E. Bakker
Head Laboratory Diagnostics sub-department
e.bakker@lumc.nl

Prof. Dr. M. H. Breuning
Head Department of Clinical Genetics
m.h.breuning@lumc.nl

Mrs. J.E.M. van Diemen-Homan
Quality Manager Genetic Counseling Section

Mrs. Drs. E. Voorhoeve
quality manager  Laboratory Diagnostics sub-department

Genetic Counselling Section

Mrs. Dr. C.J. van Asperen
head Genetic Counseling Section

Mrs. Dr. E.K. Bijlsma
clinical geneticist

Prof. Dr. M.H. Breuning
clinical geneticist

Mrs. Dr. A.H.J.T. Bröcker-Vriends
clinical geneticist

Mrs. B.T.J. van Brussel
genetic consultant

Mrs. J.E.M. van Diemen-Homan
genetic consultant

Drs. A. van Haeringen
clinical geneticist

Mrs. Drs. A.T.J.M. Helderman – v.d. Enden
clinical geneticist

Mrs. Drs. Y.M. Hendriks
medical assistant clinical genetics

Dr. F.J.H. Hes
clinical geneticist

Mrs. Drs. Y. Hilhorst-Hofstee
clinical geneticist

Mrs. Dr. N.S. den Hollander
clinical geneticist

Mrs. Dr. S.G. Kant
clinical geneticist

Mrs. Drs. M. Kriek
medical assistant clinical genetics

Mrs. Dr. S.A.M.J. Lesnik Oberstein
medical assistant clinical genetics

Mrs. A.M. van Mil
genetic consultant

Mrs. I. v.d. Schoot-van Velzen
genetic consultant in training

Mrs. Drs. F. de Snoo
medical assistant clinical genetics

Prof. Dr. A. Tibben
psychologist

 

Cytogenetics

Prof. Dr. E. Bakker
ad interim laboratory head

Mrs. Dr. K.B.M. Hansson
clinical cytogeneticist, laboratory head

Mrs. Dr. M.J.V. Hoffer
clinical cytogeneticist

Mrs. Drs. W.G.M. Kroes
clinical cytogeneticist

Mrs. Dr. C. Ruivenkamp
clinical cytogeneticist in training

Mrs. Drs. S.L. van Zelderen – Bhola
clinical cytogeneticist

Molecular Genetics

Prof. Dr. E. Bakker
laboratory head

Mrs. Dr. E.M.J. Boon
clinical molecular geneticist in training

Mrs. Dr. M.J. van Belzen
clinical molecular geneticist in training

Mrs. Dr. H.B. Ginjaar
clinical molecular geneticist

Ing. A.L.J. Kneppers
head technician

Mrs. Dr. M. Losekoot
clinical molecular geneticist, laboratory head

Mrs. Dr. C.M.J. Tops
clinical molecular geneticist

Mrs. Dr. M.M. Weiss
clinical molecular geneticist in training

Dr. J.T.H. Wijnen
clinical molecular geneticist

Hemoglobinopathies Laboratory

Dr. P.C. Giordano
clinical biochemic geneticist, laboratory head

Dr. C.L. Harteveld
clinical molecular geneticist


Publications

 Pavel S, van Nieuwpoort F, van der Meulen H, Out C, Pizinger K, Cetkovska P, Smit NP, Koerten HK.
Disturbed melanin synthesis and chronic oxidative stress in dysplastic naevi.
Eur J Cancer 2004, 40:1423-30.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15177503

Hayes MJ, Koundouris A, Gruis N, Bergman W, Peters GG, Sinclair AJ.
P16(INK4A)-independence of Epstein-Barr virus-induced cell proliferation and virus latency.
J Gen Virol. 2004, 85:1381-6.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15166419

Zuidervaart W, van der Velden PA, Hurks MH, van Nieuwpoort FA, Out-Luiting CJ, Singh AD, Frants RR, Jager MJ, Gruis NA.
Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development.
Br J Cancer. 2003, 89:1914-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14612903

de Snoo FA, Bergman W, Gruis NA.
Familial melanoma: a complex disorder leading to controversy on DNA testing.
Fam Cancer. 2003,2:109-16.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14574160

de vos tot Nederveen Cappel WH, Offerhaus GJ, van Puijenbroek M, Caspers E,Gruis NA, De Snoo FA, Lamers CB, Griffioen G, Bergman W, Vasen HF, Morreau H.
Pancreatic carcinoma in carriers of a specific 19 base pair deletion of CDKN2A/p16 (p16-leiden).
Clin Cancer Res. 2003, 9:3598-605.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14506146

van der Velden PA, Zuidervaart W, Hurks MH, Pavey S, Ksander BR, Krijgsman E, Frants RR, Tensen CP, Willemze R, Jager MJ, Gruis NA.
Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development.
Int J Cancer. 2003, 106:472-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12845640

 Gillanders E, Juo SH, Holland EA, Jones M, Nancarrow D, Freas-Lutz D, Sood R, Park N, Faruque M, Markey C, Kefford RF, Palmer J, Bergman W, Bishop DT,Tucker MA, Bressac-de Paillerets B, Hansson J, Stark M, Gruis N, Bishop JN,Goldstein AM, Bailey-Wilson JE, Mann GJ, Hayward N, Trent J; Lund Melanoma Study Group; Melanoma Genetics Consortium.
Localization of a novel melanoma susceptibility locus to 1p22.
Am J Hum Genet. 2003,73:301-13.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12844286

Pavel S, Smit NP, van der Meulen H, Kolb RM, de Groot AJ, van der Velden PA,Gruis NA, Bergman W.
Homozygous germline mutation of CDKN2A/p16 and glucose-6-phosphate dehydrogenase deficiency in a multiple melanoma case.
Melanoma Res. 2003,13:171-8.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12690301

Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N,Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA; Melanoma Genetics Consortium.
Geographical variation in the penetrance of CDKN2A mutations for melanoma.
J Natl Cancer Inst. 2002,94:894-903.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12072543

Brookes S, Rowe J, Ruas M, Llanos S, Clark PA, Lomax M, James MC, Vatcheva R, Bates S, Vousden KH, Parry D, Gruis N, Smit N, Bergman W, Peters G.
INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence.
EMBO J. 2002,21:2936-45.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12065407

Kennedy C, Naipal A, Gruis NA, Struijk L, ter Schegget J, Willemze R, Claas FH, Bouwes Bavinck JN, Doxiadis II.
MICA gene polymorphism is not associated with an increased risk for skin cancer.
J Invest Dermatol. 2002,118:686-91.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11918717

Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W, Willemze R, Bavinck JN.
Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color.
J Invest Dermatol. 2001, 117:294-300.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11511307

van der Velden PA, Sandkuijl LA, Bergman W, Pavel S, van Mourik L, Frants RR, Gruis NA.
Melanocortin-1 receptor variant R151C modifies melanoma risk in Dutch families with melanoma.
Am J Hum Genet. 2001, 69:774-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11500806

Bastiaens M, ter Huurne J, Gruis N, Bergman W, Westendorp R, Vermeer BJ,Bouwes Bavinck JN.
The melanocortin-1-receptor gene is the major freckle gene.
Hum Mol Genet. 2001, 10:1701-8.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11487574

Metzelaar-Blok JA, ter Huurne JA, Hurks HM, Keunen JE, Jager MJ, Gruis NA.
Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients.
Invest Ophthalmol Vis Sci. 2001, 42:1951-4.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11487574

van der Velden PA, Metzelaar-Blok JA, Bergman W, Monique H, Hurks H, Frants RR, Gruis NA, Jager MJ.
Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma.
Cancer Res. 2001, 61:5303-6.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11431374

Bastiaens MT, Struyk L, Tjong-A-Hung SP, Gruis N, ter Huurne J, Westendorp RG, Vermeer BJ, Bavinck JN, ter Schegget J.
Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?
Mol Carcinog. 2001, 30:56-61.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11255264

Bastiaens MT, ter Huurne JA, Kielich C, Gruis NA, Westendorp RG, Vermeer BJ, Bavinck JN; Leiden Skin Cancer Study Team.
Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair.
Am J Hum Genet. 2001, 68:884-94.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11254446

Gruis NA, Bergman W.
[From gene to disease; from p16 to melanoma].
Ned Tijdschr Geneeskd. 2000, 144:2100-2.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11103670

Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W.
Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden).
Int J Cancer. 2000, 87:809-11.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10956390

Dekker SK, van Doorn R, Kempenaar J, Gruis NA, Vermeer BJ, Ponec M.
Skin equivalent: an attractive model to evaluate early melanoma metastasis.
Melanoma Res. 2000, 10:127-40.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10803713

Gruis NA, van der Velden PA, Bergman W, Frants RR.
Familial melanoma; CDKN2A and beyond.
J Investig Dermatol Symp Proc. 1999, 4:50-4. Review.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10537008

van der Velden PA, Sandkuijl LA, Bergman W, Hille ET, Frants RR, Gruis NA.
A locus linked to p16 modifies melanoma risk in Dutch familial atypical multiple mole melanoma (FAMMM) syndrome families.
Genome Res. 1999,9:575-80.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10400925

Snels DG, Hille ET, Gruis NA, Bergman W.
Risk of cutaneous malignant melanoma in patients with nonfamilial atypical nevi from a pigmented lesions clinic.
J Am Acad Dermatol. 1999, 40:686-93.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10321594

Latvian Biomedical Research and Study Centre

Our institution

Latvian Biomedical Research and Study Centre
Ratsupites 1
Riga LV-1067
Latvia

E-mail: zina@biomed.lu.lv


Our group

Laboratory of Melanoma Research
Latvian Biomedical Research and Study Centre
Ratsupites 1
Riga LV-1067
Latvia

Latvian Oncological Center
(Clinic)
Hipocrata 4
Riga LV-1038
Latvia


The Group leader

Olita Heisele, PhD
Latvian Biomedical Research and Study Centre
Ratsupites 1
Riga LV-1067
Latvia

E-mail: olita@biomed.lu.lv
Phone: 371-67808215
Fax: 371-67442407


Group description

Laboratory of Melanoma Research is focused on two main lines of research:
1) melanoma genetic and
2) melanoma immunogenetics and immunology

1. Recently the melanoma research group has focused on genetic background in melanoma development and we are registering melanoma families in Latvia. The group is involved in screening of melanoma susceptibility genes CDKN2A/ARF and CDK4 for their mutations. We have revealed two CDK4 R24H mutation positive families and follow up studies are going on. The group is involved in the analysis of the MC1R gene as a modifier of melanoma risk. We are collaborating with the Genome Database of Latvian Population and Latvian Oncological center.

2. Our melanoma immunogenetic studies are associated with the research on melanoma associated antigen (MAA) expression obtained in surgical samples. MAA profile of definite antigens (MAGE genes, MART, tyrosinaze, gp 100) was studied in accordance with clinical and histopathological features of tumour and patients surveillance.

3. The experimental study of MAA expression pattern in melanoma cell cultures after treatment with two different biomodulators elaborated in Latvia – Lariphan and Rigvir is carried out. Lariphan is double-stranded RNA of natural origin with interferon-inducing, antiviral, antitumoral effects. Rigvir is biomodulator of viral origin with immunomodulating, antitumoral and cytolytic effects.


Related Links

Latvian Biomedical Research and Study Centre
http://bmc.biomed.lu.lv.


The names and e-mail addresses of group members with a description of their contribution

Scientific team leader

Olita Heisele, PhD
olita@biomed.lu.lv

Clinical team leader

Ludmila Engele, PhD
ludmila.engele@gmail.com

Experienced Researchers

Dace Pjanova
dace@biomed.lu.lv

Baiba Streinerte, LOC
baiba.streinerte@aslimnica.lv

Dermatologist

Kristine Azariana

Technicians

Ingrida Desjatnikova, BMC (nurse)
ingrida@biomed.lu.lv

Vesma Matroze, LOC (nurse)

Student

Aija Ozola


Publications

Pjanova D, Heisele O, Engele L, Randerson-Moor JA, Harland M, Bishop DT, Newton Bishop JA, Taylor C, Debniak T, Lubinski J, Kleina R.
CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population.
Melanoma Res. 2007; 17 (3): 185-192.

Pjanova D, Heisele O, Engele L, Randerson-Moor JA, Kukalizch K, Bishop DT, Newton Bishop JA.
Analysis of Latvian melanoma families for 9p21 germline deletions by multiplex ligation-dependent probe amplification approach.
Acta Universitatis Latviensis. 2006; 710: 7-16.

Pjanova D, Engele L, Ignatovica V and Heisele O.
CDKN2A mutations and loss of heterozygosity in primary melanomas.
Proc. Latvian Acad. Sci. Section B. 2006; 60 (2/3): 98-100.

Pjanova D, Heisele O, Engele L, Desjatnikova I.
Tumour suppressor gene CDKN2A/p16 germline mutations in melanoma patients with additional cancer and cancer in their family history.
Acta Universitatis Latviensis. 2003, 662: 25-32.

Heisele O, Ferdats A, Engele L, Rupais A, Desjatnikova I.
Melanoma associated antigens as markers for melanoma progression and efficiacy of immunotherapy.
J.Tumour Marker Oncology. 2000, 15: 147-153.

Heisele O, Ferdats A, Engele L.
Melanoma associated antigens as additional markers of tumour progression.
J.Tumour Marker Oncology, 2000, 15: 147-153.

Pjanova D, Heisele O, Engele L, Balkovska I, Desjatnikova I, Ignatovica V.
CDKN2A/ARF and CDK4 germline alterations in sporadic cutaneous malignant melanoma patients of Latvian population.
In press.

Click here to see a PDF of this publication

GenoMEL (Latin America)

Coordinator

Dr Francisco Cuellar
facuellar@yahoo.com

Supervisor

Dr Susana Puig
spuig@clinic.ub.es


For the past three years we have been identifying cases of familial melanoma and multiple primary melanoma in Latin America. Both data and samples have been gathered for use in studies of CDKN2A (p16/p14ARF), CDK4 and MC1R at the Molecular Genetics Laboratory (MGL) of the Hospital Clnic of Barcelona (HCB).

This work is ongoing and we are anticipating a series of publications in 2009/2010.


Leaders in participant countries

Argentina

Dr Horacio Cabo
hcabo@sad.org.ar

Brazil

Dr Gilles Landman
glandman@terra.com.br

Chile

Dr Enrique Morales and Dr Claudia Balestrini
claubal@vtr.net

 Colombia

Dr Cesar Merlano
merlano@col.net.co

Mexico

Dr Blanca Carlos and Julio Salas
blancarlos_1@hotmail.com
jsalas@fm.uanl.mx

Uruguay

Dr Alejandra Larre-Borges
alarreborges@gmail.com


Presentations (a brief selection)

Genetic risk factors for melanoma development in Latin America
Presented at the 16th European Academy of Dermatology and Venereology (EADV) Congress, Vienna, Austria, May 2007 and the 20th World Congress of Dermatology, Buenos Aires, Argentina, October 2007.

Report of a novel CDKN2A germ line mutation in two melanoma prone families from Uruguay
Presented at the 21st World Congress of Dermatology, Buenos Aires, Argentina, October 2007. This work received an award as one of the top three poster presentations.

Interview about GenoMEL project
Presented on the Uruguayan TV show: “Calidad de Vida”. (Dr. Larre-Borges, Montevideo, Uruguay, December 2008).