1. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma.
- Author
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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, and Meltzer SJ
- Subjects
- Adenocarcinoma metabolism, Adenocarcinoma pathology, Barrett Esophagus metabolism, Barrett Esophagus pathology, Base Sequence, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, China, Esophageal Neoplasms metabolism, Esophageal Neoplasms pathology, Geography, Head and Neck Neoplasms metabolism, Head and Neck Neoplasms pathology, Humans, Mutation, North America, Receptor, Notch1 genetics, Receptor, Notch2 genetics, Receptor, Notch3, Receptors, Notch genetics, Sequence Analysis, DNA, Squamous Cell Carcinoma of Head and Neck, Tumor Suppressor Protein p53 genetics, Adenocarcinoma genetics, Barrett Esophagus genetics, Carcinoma, Squamous Cell genetics, Esophageal Neoplasms genetics, Exome, Head and Neck Neoplasms genetics
- Abstract
Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) 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 esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus.
- Published
- 2012
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