In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2022-1-27), p. e0262419-
Abstract:
Genetic predisposition accounts for nearly 10% of all melanoma cases and has been associated with a dozen moderate- to high-penetrance genes, including CDKN2A , CDK4 , POT1 and BAP1 . However, in most melanoma-prone families, the genetic etiology of cancer predisposition remains undetermined. The goal of this study was to identify rare genomic variants associated with cutaneous melanoma susceptibility in melanoma-prone families. Whole-exome sequencing was performed in 2 affected individuals of 5 melanoma-prone families negative for mutations in CDKN2A and CDK4 , the major cutaneous melanoma risk genes. A total of 288 rare coding variants shared by the affected relatives of each family were identified, including 7 loss-of-function variants. By performing in silico analyses of gene function, biological pathways, and variant pathogenicity prediction, we underscored the putative role of several genes for melanoma risk, including previously described genes such as MYO7A and WRN , as well as new putative candidates, such as SERPINB4 , HRNR , and NOP10 . In conclusion, our data revealed rare germline variants in melanoma-prone families contributing with a novel set of potential candidate genes to be further investigated in future studies.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0262419
DOI:
10.1371/journal.pone.0262419.g001
DOI:
10.1371/journal.pone.0262419.g002
DOI:
10.1371/journal.pone.0262419.g003
DOI:
10.1371/journal.pone.0262419.t001
DOI:
10.1371/journal.pone.0262419.t002
DOI:
10.1371/journal.pone.0262419.t003
DOI:
10.1371/journal.pone.0262419.t004
DOI:
10.1371/journal.pone.0262419.t005
DOI:
10.1371/journal.pone.0262419.t006
DOI:
10.1371/journal.pone.0262419.s001
DOI:
10.1371/journal.pone.0262419.s002
DOI:
10.1371/journal.pone.0262419.s003
DOI:
10.1371/journal.pone.0262419.s004
DOI:
10.1371/journal.pone.0262419.s005
DOI:
10.1371/journal.pone.0262419.s006
DOI:
10.1371/journal.pone.0262419.s007
DOI:
10.1371/journal.pone.0262419.s008
DOI:
10.1371/journal.pone.0262419.s009
DOI:
10.1371/journal.pone.0262419.s010
DOI:
10.1371/journal.pone.0262419.r001
DOI:
10.1371/journal.pone.0262419.r002
DOI:
10.1371/journal.pone.0262419.r003
DOI:
10.1371/journal.pone.0262419.r004
DOI:
10.1371/journal.pone.0262419.r005
DOI:
10.1371/journal.pone.0262419.r006
DOI:
10.1371/journal.pone.0262419.r007
DOI:
10.1371/journal.pone.0262419.r008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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