Abstract
BackgroundGastric cancer is one of the leading cancer types in incidence and mortality, especially in Asia. In order to improve survival, identification of a catalogue of molecular alterations underlying gastric cancer is a critical step for developing and designing genome-directed therapies.Methodology/Principal FindingsThe Center for Cancer Genome Discovery (CCGD) at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection platform, termed OncoMap v4, interrogates 474 “hotspot” mutations in 41 genes that are relevant for cancer. We performed OncoMap v4 in formalin-fixed paraffin-embedded (FFPE) tissue specimens from 237 gastric adenocarcinomas. Using OncoMap v4, we found that 34 (14.4%) of 237 gastric cancer patients harbored mutations. Among mutations we screened, PIK3CA mutations were the most frequent (5.1%) followed by p53 (4.6%), APC (2.5%), STK11 (2.1%), CTNNB1 (1.7%), and CDKN2A (0.8%). Six samples harbored concomitant somatic mutations. Mutations of CTNNB1 were significantly more frequent in EBV-associated gastric carcinoma (P = 0.046). Our study led to the detection of potentially druggable mutations in gastric cancer which may guide novel therapies in subsets of gastric cancer patients.Conclusions/SignificanceUsing high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma.
Highlights
Gastric cancer is the fourth most common cause of cancer worldwide, and the second leading cause of cancer deaths worldwide
Conclusions/Significance: Using high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma
Recent exome sequencing of gastric adenocarcinoma showed that samples with microsatellite instability (MSI) had an average of 31.61 somatic mutations per megabase of DNA, whereas the microsatellite-stable (MSS) gastric cancer samples had an average of 3.29, a difference of approximately tenfold
Summary
Gastric cancer is the fourth most common cause of cancer worldwide, and the second leading cause of cancer deaths worldwide. [1] Despite recent efforts in multimodality therapeutic approach for advanced gastric cancer, approximately half of patients who undergo curative surgical resection still develop loco-regional or distant metastases and die from the disease.[2,3,4]. Precise molecular subclassifications as well as a full landscape of oncogenic driver mutations have not been defined yet in gastric cancer. [7,8] We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer oncogenes and tumor suppressor genes to identify the subsets of gastric cancer patients who may potentially benefit from targeted therapy (Table 1). In order to improve survival, identification of a catalogue of molecular alterations underlying gastric cancer is a critical step for developing and designing genome-directed therapies
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