Open AccessSearching for the missing genetic determinants of hereditary breast cancer risk by whole-exome sequencing of BRCA-negative patients: new candidate genes USP39, SLIT3, CREB3
Author(s) -
Кирилл Загороднев,
Alexandr A. Romanko,
Юлий Андреевич Горгуль,
Александр Иванцов,
Anna P. Sokolenko,
Ilya V. Bizin,
Ekatherina Sh. Kuligina
Publication year - 2021
Publication title -
voprosy onkologii
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.108
H-Index - 11
eISSN - 2949-4915
pISSN - 0507-3758
DOI - 10.37469/0507-3758-2021-67-1-111-116
Subject(s) - exome sequencing , candidate gene , sanger sequencing , genetics , breast cancer , mutation , gene , exome , cancer , germline , biology , germline mutation , dna sequencing , computational biology , bioinformatics , medicine
The search for the new hereditary mutations and a precise molecular genetic diagnosis that determines the causative mutation in each specific case of hereditary breast cancer (BC) is a clinically important task since it helps to define the personal therapeutic approach and increase the effectiveness of preventive measures. Using whole-exome sequencing (WES) we analyzed the full spectrum of hereditary variations in 49 Russian patients with clinical signs of a hereditary disease which allowed us to compile a list of 229 candidate probably pathogenic germ-line variants. Then, the selected candidate mutations were validated by Sanger sequencing and molecular-epidemiological studies, the predisposing roles of three oncologically relevant mutations (USP39 c.*208G>C, SLIT3 p.Arg154Cys, and CREB3 p.Lys157Glu) were confirmed. Our candidate genes are first mentioned in connection with the hereditary risk of BC. The final proofs of the causative roles of these variants could be obtained through functional tests as well as via the analysis of the mutations segregation in BC families.