Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations

Importance The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previousl...

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Autores: Potrony Mateu, Míriam, Puig Butillé, Joan Anton, Aguilera, Paula, Badenas Orquin, Celia, Tell Martí, Gemma, Carrera Álvarez, Cristina, Del Pozo, Luis Javier, Conejo Mir, Julian, Malvehy, J. (Josep), Puig i Sardà, Susana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/113903
Acceso en línea:https://hdl.handle.net/2445/113903
Access Level:acceso abierto
Palabra clave:Melanoma
Fenotip
Càncer
Genètica mèdica
Càncer de ronyó
Phenotype
Cancer
Medical genetics
Renal cancer
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repository_id_str
spelling Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutationsPotrony Mateu, MíriamPuig Butillé, Joan AntonAguilera, PaulaBadenas Orquin, CeliaTell Martí, GemmaCarrera Álvarez, CristinaDel Pozo, Luis JavierConejo Mir, JulianMalvehy, J. (Josep)Puig i Sardà, SusanaMelanomaFenotipCàncerGenètica mèdicaCàncer de ronyóMelanomaPhenotypeCancerMedical geneticsRenal cancerImportance The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previously assessed in a single cohort of Spanish patients with melanoma or in p16INK4A mutation carriers.Objectives To evaluate the prevalence of MITF p.E318K in Spanish patients with melanoma and assess the association with clinical and phenotypic features.Design, Setting, and Participants A hospital-based, case-control study was conducted at the Melanoma Unit of Hospital Clinic of Barcelona, with MITF p.E318K genotyped in all patients using TaqMan probes. We included 531 patients: 271 patients with multiple primary melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families with a single melanoma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carrying CDKN2A mutations affecting p16INK4A. A population-based series of 499 age- and sex-matched cancer-free individuals from the Spanish National Bank of DNA were included as controls. Patients were recruited between January 1, 1992, and June 30, 2014; data analysis was conducted from September 1 to November 30, 2014.Main Outcomes and Measures The genetic results of the MITF p.E318K variant were correlated with clinical and phenotypic features.Results Among the 531 patients, the prevalence of the MITF p.E318K variant was calculated among the different subsets of patients included and was 1.9% (9 of 462) in all melanoma patients with wild-type p16INK4A, 2.6% (7 of 271) in those with MPM, and 2.9% (2 of 69) in the probands of families with p16INK4A mutations. With results reported as odds ratio (95% CI), the MITF p.E318K was associated with an increased melanoma risk (3.3 [1.43-7.43]; P < .01), especially in MPM (4.5 [1.83-11.01]; P < .01) and high nevi count (>200 nevi) (8.4 [2.14-33.19]; P < .01). Two fast-growing melanomas were detected among 2 MITF p.E318K carriers during dermatologic digital follow-up.Conclusions and Relevance In addition to melanoma risk, MITF p.E318K is associated with a high nevi count and could play a role in fast-growing melanomas. Testing for MITF p.E318K should not exclude patients with known mutations in p16INK4A. Strict dermatologic surveillance, periodic self-examination, and renal cell carcinoma surveillance should be encouraged in this context.American Medical Association2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/113903Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1001/jamadermatol.2015.4356JAMA Dermatology, 2015, vol. 152, num. 4, p. 405-412https://doi.org/10.1001/jamadermatol.2015.4356(c) American Medical Association, 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1139032026-05-27T06:46:51Z
dc.title.none.fl_str_mv Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
title Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
spellingShingle Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
Potrony Mateu, Míriam
Melanoma
Fenotip
Càncer
Genètica mèdica
Càncer de ronyó
Melanoma
Phenotype
Cancer
Medical genetics
Renal cancer
title_short Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
title_full Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
title_fullStr Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
title_full_unstemmed Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
title_sort Prevalence of MITF p.E318K in patients with melanoma independent of the presence of CDKN2A causative mutations
dc.creator.none.fl_str_mv Potrony Mateu, Míriam
Puig Butillé, Joan Anton
Aguilera, Paula
Badenas Orquin, Celia
Tell Martí, Gemma
Carrera Álvarez, Cristina
Del Pozo, Luis Javier
Conejo Mir, Julian
Malvehy, J. (Josep)
Puig i Sardà, Susana
author Potrony Mateu, Míriam
author_facet Potrony Mateu, Míriam
Puig Butillé, Joan Anton
Aguilera, Paula
Badenas Orquin, Celia
Tell Martí, Gemma
Carrera Álvarez, Cristina
Del Pozo, Luis Javier
Conejo Mir, Julian
Malvehy, J. (Josep)
Puig i Sardà, Susana
author_role author
author2 Puig Butillé, Joan Anton
Aguilera, Paula
Badenas Orquin, Celia
Tell Martí, Gemma
Carrera Álvarez, Cristina
Del Pozo, Luis Javier
Conejo Mir, Julian
Malvehy, J. (Josep)
Puig i Sardà, Susana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Melanoma
Fenotip
Càncer
Genètica mèdica
Càncer de ronyó
Melanoma
Phenotype
Cancer
Medical genetics
Renal cancer
topic Melanoma
Fenotip
Càncer
Genètica mèdica
Càncer de ronyó
Melanoma
Phenotype
Cancer
Medical genetics
Renal cancer
description Importance The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previously assessed in a single cohort of Spanish patients with melanoma or in p16INK4A mutation carriers.Objectives To evaluate the prevalence of MITF p.E318K in Spanish patients with melanoma and assess the association with clinical and phenotypic features.Design, Setting, and Participants A hospital-based, case-control study was conducted at the Melanoma Unit of Hospital Clinic of Barcelona, with MITF p.E318K genotyped in all patients using TaqMan probes. We included 531 patients: 271 patients with multiple primary melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families with a single melanoma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carrying CDKN2A mutations affecting p16INK4A. A population-based series of 499 age- and sex-matched cancer-free individuals from the Spanish National Bank of DNA were included as controls. Patients were recruited between January 1, 1992, and June 30, 2014; data analysis was conducted from September 1 to November 30, 2014.Main Outcomes and Measures The genetic results of the MITF p.E318K variant were correlated with clinical and phenotypic features.Results Among the 531 patients, the prevalence of the MITF p.E318K variant was calculated among the different subsets of patients included and was 1.9% (9 of 462) in all melanoma patients with wild-type p16INK4A, 2.6% (7 of 271) in those with MPM, and 2.9% (2 of 69) in the probands of families with p16INK4A mutations. With results reported as odds ratio (95% CI), the MITF p.E318K was associated with an increased melanoma risk (3.3 [1.43-7.43]; P < .01), especially in MPM (4.5 [1.83-11.01]; P < .01) and high nevi count (>200 nevi) (8.4 [2.14-33.19]; P < .01). Two fast-growing melanomas were detected among 2 MITF p.E318K carriers during dermatologic digital follow-up.Conclusions and Relevance In addition to melanoma risk, MITF p.E318K is associated with a high nevi count and could play a role in fast-growing melanomas. Testing for MITF p.E318K should not exclude patients with known mutations in p16INK4A. Strict dermatologic surveillance, periodic self-examination, and renal cell carcinoma surveillance should be encouraged in this context.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/113903
url https://hdl.handle.net/2445/113903
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1001/jamadermatol.2015.4356
JAMA Dermatology, 2015, vol. 152, num. 4, p. 405-412
https://doi.org/10.1001/jamadermatol.2015.4356
dc.rights.none.fl_str_mv (c) American Medical Association, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Medical Association, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Medical Association
publisher.none.fl_str_mv American Medical Association
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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