High-Throughput Mutation Profiling Identifies Frequent Somatic Mutations in Advanced Gastric Adenocarcinoma

作者：Lee Jeeyun^*; van Hummelen Paul; Go Christina; Palescandolo Emanuele; Jang Jiryeon; Park Ha Young; Kang So Young; Park Joon Oh; Kang Won Ki; MacConaill Laura; Kim Kyoung Mee

来源：PLos One, 2012, 7(6): e38892.

DOI：10.1371/journal.pone.0038892

Background: Gastric 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. %26lt;br%26gt;Methodology/Principal Findings: The 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 %26quot;hotspot%26apos;%26apos; 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. %26lt;br%26gt;Conclusions/Significance: Using high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma.

• 出版日期2012-6-18