Gene mutations distinguishing gastric from colorectal and esophageal adenocarcinomas.

Abstract

424 Background: Genetic analysis of gastrointestinal malignancies shows a great number of mutations. Most mutations found in gastric tumors are found in colorectal and esophageal tumors, and vice versa. The challenge remains to identify mutations that distinguish gastric from colorectal and esophageal cancers. Using open-access cancer genomics data, we sought to identify mutations that accounted for the unique phenotypic features of gastric tumors. Methods: Thirteen cancer genomics datasets with demographic, clinical, and genetic variables were analyzed. Each subject was flagged with or without a mutated gene. For each anatomical location, pathologic stage and histology were compared between subjects with and without a specific mutated gene, using two-sample t tests, adjusted for multiple gene testing. Results: Analysis included 1,915 subjects with valid pathologic stage and histology. Mean age was 68 years (SD=10). About 54% were female. The most common race was Caucasian (37%) while minorities were rare with high rate of missing data (44%). Pathologic stage: 20% stage I, 35% stage II, 31% stage III, and 14% stage IV. Anatomical location: 29.5% gastric, 59.5% colorectal, and 11.0% esophageal. Histology of gastric cancer: 61.4% intestinal, 23.2% diffuse, 14.9% others, and 0.5% missing. One gene–HEATR7B2–though rarely mutated, occurred only in stage IV of gastric tumors. Two mutated genes–CDH1, RHOA–distinguished diffuse from intestinal gastric histology. One mutated gene–CDH1–distinguished gastric from colorectal and esophageal tumors. Conclusions: This study confirmed the genes involved in the pathogenesis of gastric malignancies (CDH1, RHOA) and linked one novel gene to stage IV of gastric tumors (HEATR7B2). Future animal and human epidemiologic studies are needed to elucidate how this novel gene contributes to gastric malignancies.