Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma.
Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma.
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DOI：
10.1158/2159-8290.cd-12-0189
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发表时间：
2012-10
期刊：
影响因子：
28.2
通讯作者：
Meltzer SJ
中科院分区：
文献类型：
--
作者：
Agrawal N;Jiao Y;Bettegowda C;Hutfless SM;Wang Y;David S;Cheng Y;Twaddell WS;Latt NL;Shin EJ;Wang LD;Wang L;Yang W;Velculescu VE;Vogelstein B;Papadopoulos N;Kinzler KW;Meltzer SJ
食管癌（EC）在癌症死亡中排名第六。为了探索其遗传起源，我们对来自美国的11例腺癌（EAC）和12例鳞状细胞癌（ESCC）进行了外显子组测序。有趣的是，在21%的ESCC中发现了NOTCH 1的失活突变，但在EAC中没有发现。在突变谱中存在显著差异，在ESCC中具有更多的插入缺失，在EAC中A：T>C：G颠换，并且在ESCC中C：G>G：C颠换（p<0.0001）。值得注意的是，NOTCH 1突变在北美ESCC中（53例中的11例）比在中国ESCC中（48例中的1例）更频繁。一项平行分析发现，EAC中的大多数突变已经存在于匹配的巴雷特食管（BE）中。这些发现突出了EAC和ESCC，美国和中国ESCC之间的关键遗传差异，并表明NOTCH 1是食管中的肿瘤抑制基因。最后，我们提供了一个遗传基础的进化EAC从BE。
Esophageal cancer (EC) ranks sixth in cancer death. To explore its genetic origins, we performed exomic sequencing on 11 adenocarcinomas (EAC) and 12 squamous cell carcinomas (ESCCs) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (p<0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett’s esophagus (BE). These discoveries highlight key genetic differences between EAC and ESCC, American and Chinese ESCC, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from BE.