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

被引：63

作者：

Lee, Jeeyun ^{[1
]}

van Hummelen, Paul ^{[2
,3
]}

Go, Christina ^{[2
,3
]}

Palescandolo, Emanuele ^{[2
,3
]}

Jang, Jiryeon ^{[1
]}

Park, Ha Young ^{[4
]}

Kang, So Young ^{[4
]}

Park, Joon Oh ^{[1
]}

Kang, Won Ki ^{[1
]}

MacConaill, Laura ^{[2
,3
]}

Kim, Kyoung-Mee ^{[4
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea

[2] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea

来源：

PLOS ONE | 2012年 / 7卷 / 06期

关键词：

CANCER; GENE; PIK3CA; P53;

D O I：

10.1371/journal.pone.0038892

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. 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 "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/Significance: Using high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma.

引用

页数：5