Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer

Ruta Sahasrabudhe, Paul Lott, Mabel Bohorquez, Ted Toal, Ana P. Estrada, John J. Suarez, Alejandro Brea-Fernández, José Cameselle-Teijeiro, Carla Pinto, Irma Ramos, Alejandra Mantilla, Rodrigo Prieto, Alejandro Corvalan, Enrique Norero, Carolina Alvarez, Teresa Tapia, Pilar Carvallo, Luz M. Gonzalez, Alicia Cock-Rada, Angela SolanoFlorencia Neffa, Adriana Della Valle, Chris Yau, Gabriela Soares, Alexander Borowsky, Nan Hu, Li Ji He, Xiao You Han, Magdalena Echeverry, Mabel Bohorquez, Rodrigo Prieto, John Suarez, Gilbert Mateus, Maria Mercedes Bravo, Fernando Bolaños, Alejandro Vélez, Alejandro Corvalan, Pilar Carvallo, Javier Torres, Luis G. Carvajal-Carmona, Philip R. Taylor, Alisa M. Goldstein, Clara Ruiz-Ponte, Manuel R. Teixeira

    Research output: Contribution to journalArticle in an indexed scientific journalpeer-review

    94 Scopus citations


    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.

    Original languageEnglish
    Pages (from-to)983-986.e6
    Issue number5
    StatePublished - 1 Apr 2017

    Bibliographical note

    Publisher Copyright:
    © 2017 AGA Institute


    • Interaction
    • Stomach
    • Tumor
    • WES


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