Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
PLoS One. 2012;7(6):e38892. doi: 10.1371/journal.pone.0038892. Epub 2012 Jun 18.
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.
胃癌是发病率和死亡率最高的癌症类型之一，尤其在亚洲。为了提高生存率，确定胃癌相关的分子改变目录是开发和设计基因组导向治疗的关键步骤。
方法/主要发现：达纳-法伯癌症研究所（DFCI）的癌症基因组发现中心（CCGD）已经采用了高通量基因分型平台来确定大量已知癌症基因的突变状态。该突变检测平台称为 OncoMap v4，可检测 41 个与癌症相关的基因中的 474 个“热点”突变。我们在 237 例福尔马林固定石蜡包埋（FFPE）的胃腺癌组织标本中进行了 OncoMap v4 检测。使用 OncoMap v4，我们发现 237 例胃癌患者中有 34 例（14.4％）存在突变。在我们筛选的突变中，PIK3CA 突变最为常见（5.1％），其次是 p53（4.6％），APC（2.5％），STK11（2.1％），CTNNB1（1.7％）和 CDKN2A（0.8％）。六个样本同时存在体细胞突变。EBV 相关胃癌中 CTNNB1 突变明显更为频繁（P = 0.046）。我们的研究发现了胃癌中潜在的可用药突变，这可能为部分胃癌患者提供新的治疗方法。
结论/意义：使用高通量突变筛选平台，我们发现 PIK3CA 突变是胃腺癌最常见的靶标。
