Germline Cancer Susceptibility in Individuals with Melanoma.
Cancer Predisposition
DNA Repair
Familial Melanoma
Family History
Genetic Testing
Germline
Homologous Repair Deficiency
Inherited Cancer Syndromes
Melanoma
Journal
Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132
Informations de publication
Date de publication:
19 Mar 2024
19 Mar 2024
Historique:
received:
19
05
2023
revised:
05
11
2023
accepted:
27
11
2023
medline:
22
3
2024
pubmed:
22
3
2024
entrez:
21
3
2024
Statut:
aheadofprint
Résumé
Prior studies have estimated a small number of individuals with melanoma (2-2.5%) have germline cancer predisposition, yet a recent twin study suggested melanoma has the highest hereditability among cancers. To determine the incidence of hereditary melanoma and characterize the spectrum of cancer predisposition genes that may increase the risk of melanoma. 400 individuals with melanoma and personal or family history of cancers underwent germline testing of >80 cancer predisposition genes. Comparative analysis of germline data was performed on 3 additional oncologic and dermatologic datasets. Germline pathogenic/likely pathogenic (P/LP) variants were identified in 15.3% (61) individuals with melanoma. Most variants (41, 67%) involved genes considered unrelated to melanoma (BLM, BRIP1, CHEK2, MLH1, MSH2, PMS2, RAD51C). A third (20, 33%) were in genes previously associated with familial melanoma (BAP1, BRCA2, CDKN2A, MITF, TP53). Nearly half (30, 46.9%) of P/LP variants were in HRD genes. Validation cohorts demonstrated P/LP rates of 10.6% from an unselected oncologic cohort, 15.8% from a selected commercial testing cohort and 14.5% from a highly selected dermatologic study. Cohorts with varying degrees of selection, some retrospective. Germline predisposition in individuals with melanoma is common, with clinically actionable findings diagnosed in 10.6% to 15.8%.
Sections du résumé
BACKGROUND
BACKGROUND
Prior studies have estimated a small number of individuals with melanoma (2-2.5%) have germline cancer predisposition, yet a recent twin study suggested melanoma has the highest hereditability among cancers.
OBJECTIVE
OBJECTIVE
To determine the incidence of hereditary melanoma and characterize the spectrum of cancer predisposition genes that may increase the risk of melanoma.
METHODS
METHODS
400 individuals with melanoma and personal or family history of cancers underwent germline testing of >80 cancer predisposition genes. Comparative analysis of germline data was performed on 3 additional oncologic and dermatologic datasets.
RESULTS
RESULTS
Germline pathogenic/likely pathogenic (P/LP) variants were identified in 15.3% (61) individuals with melanoma. Most variants (41, 67%) involved genes considered unrelated to melanoma (BLM, BRIP1, CHEK2, MLH1, MSH2, PMS2, RAD51C). A third (20, 33%) were in genes previously associated with familial melanoma (BAP1, BRCA2, CDKN2A, MITF, TP53). Nearly half (30, 46.9%) of P/LP variants were in HRD genes. Validation cohorts demonstrated P/LP rates of 10.6% from an unselected oncologic cohort, 15.8% from a selected commercial testing cohort and 14.5% from a highly selected dermatologic study.
LIMITATIONS
CONCLUSIONS
Cohorts with varying degrees of selection, some retrospective.
CONCLUSION
CONCLUSIONS
Germline predisposition in individuals with melanoma is common, with clinically actionable findings diagnosed in 10.6% to 15.8%.
Identifiants
pubmed: 38513832
pii: S0190-9622(24)00504-8
doi: 10.1016/j.jaad.2023.11.070
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.