1. Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer.
- Author
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Sahasrabudhe R, Lott P, Bohorquez M, Toal T, Estrada AP, Suarez JJ, Brea-Fernández A, Cameselle-Teijeiro J, Pinto C, Ramos I, Mantilla A, Prieto R, Corvalan A, Norero E, Alvarez C, Tapia T, Carvallo P, Gonzalez LM, Cock-Rada A, Solano A, Neffa F, Della Valle A, Yau C, Soares G, Borowsky A, Hu N, He LJ, Han XY, Taylor PR, Goldstein AM, Torres J, Echeverry M, Ruiz-Ponte C, Teixeira MR, and Carvajal-Carmona LG
- Subjects
- Aged, Aged, 80 and over, Fanconi Anemia Complementation Group N Protein, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Male, Middle Aged, Mutation, Recombinational DNA Repair genetics, BRCA1 Protein genetics, DNA-Binding Proteins genetics, Nuclear Proteins genetics, Stomach Neoplasms genetics, Tumor Suppressor Proteins genetics
- Abstract
Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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