Génétique et mélanomes multiples : Caractérisation génétique d'une population atteinte de mélanomes multiples

Details

Supervisors

De Leener, Anne ; Tromme, Isabelle

Faculty

Faculté de médecine et médecine dentaire

Degree label

Master [180] en médecine

Abstract

enA melanoma is a deadly cancer whose incidence keeps increasing. The study of genetic mutations predisposing to melanoma aims at identifying patients carrying these mutations in order for them to benefit from adequate prevention and monitoring measures. CDKN2A, CDK4, BAP1, MITF, and MC1R, the genes predisposing to melanoma, will be of great interest in this paper. This study is based on 63 patients who have developed at least two melanomas during their lifetime. The first part intends to analyse the prevalence of the genetic mutations in CDKN2A, CDK4, BAP1, MITF, and MC1R in our cohort versus in that of the general population. The second part of this paper aims at studying risk factors for melanoma in the cohort of patients carrying the genetic mutations in CDKN2A, CDK4, BAP1, MITF, and MC1R versus in that of patients who do not carry such mutations. The prevalence of the p.Ser83Pro, p.Asp84Glu, p.Leu132Phe, p.Ile155Thr and p.Arg306His (MC1R), p.Gly67Arg and p.His158Asp (CDKN2A), and p.Glu318Lys (MITF) variants is substantially higher in our cohort than in the control population. However, no such results have been observed in the p.Asp294His and p.Arg151Cys (MC1R) variants. Patients with mutations in the CDKN2A gene developed their first melanoma on average seven years earlier than non-mutated patients. The prevalence of the studied mutations is significantly higher in patients with a light phototype and many nevi than in patients with dark skin and few nevi. No significantly different results have been observed between the two groups with respect to gender, history of UV exposure and personal and family oncological history. This study shows a link between a range of mutations (some are known to be pathogenic, others not) and the development of melanomas. Nevertheless, the nature of this link remains unclear. The phototype, the number of nevi, and the patient’s age when his/her first melanoma appears seem to be clues to the presence of a mutation predisposing to melanoma. However, as our results show, these criteria are not sufficient to guess the genetic status of the patient. Our observations therefore support the usefulness of genetic analyses in this case. Finally, this paper brings back into focus the following question: when should a genetic analysis be proposed to a patient with melanomas?