Sahasrabudhe Ruta, Lott Paul, Bohorquez Mabel, Toal Ted, Estrada Ana P, Suarez John J, Brea-Fernández Alejandro, Cameselle-Teijeiro José, Pinto Carla, Ramos Irma, Mantilla Alejandra, Prieto Rodrigo, Corvalan Alejandro, Norero Enrique, Alvarez Carolina, Tapia Teresa, Carvallo Pilar, Gonzalez Luz M, Cock-Rada Alicia, Solano Angela, Neffa Florencia, Della Valle Adriana, Yau Chris, Soares Gabriela, Borowsky Alexander, Hu Nan, He Li-Ji, Han Xiao-You, Taylor Philip R, Goldstein Alisa M, Torres Javier, Echeverry Magdalena, Ruiz-Ponte Clara, Teixeira Manuel R, Carvajal-Carmona Luis G
Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California.
Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia.
Gastroenterology. 2017 Apr;152(5):983-986.e6. doi: 10.1053/j.gastro.2016.12.010. Epub 2016 Dec 23.
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.
高达10%的胃癌病例是家族性的，但到目前为止，只有CDH1基因的突变与胃癌风险相关。为了确定影响胃癌风险的基因变异，我们收集了28例与CDH1基因突变无关的遗传性弥漫性胃癌（HDGC）患者的血液样本，并进行了全外显子测序分析。然后，我们分析了333例独立的HDGC和非HDGC病例中候选基因的序列。我们在调控同源DNA重组的PALB2、BRCA1或RAD51C基因中鉴定出11例突变。我们在31例HDGC患者中的2例（6.5%）和331例散发性胃癌患者中的9例（2.8%）发现了这些突变。在我们的研究中，这些突变大多先前已与其他类型的肿瘤相关，并且部分与胃癌共分离。发生在这些突变患者身上的肿瘤具有与体细胞同源重组缺陷相关的突变特征。我们的研究结果表明，同源重组缺陷会增加胃癌风险。
