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.