Faculty Collaboration Database

Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov 2012 Oct;2(10):899-905

Date

08/11/2012

Pubmed ID

22877736

Pubmed Central ID

PMC3473124

DOI

10.1158/2159-8290.CD-12-0189

Scopus ID

2-s2.0-84867398217 (requires institutional sign-in at Scopus site)   296 Citations

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.

Author List

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

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Barrett Esophagus
Base Sequence
Carcinoma, Squamous Cell
China
Esophageal Neoplasms
Exome
Geography
Head and Neck Neoplasms
Humans
Mutation
North America
Receptor, Notch1
Receptor, Notch2
Receptor, Notch3
Receptors, Notch
Sequence Analysis, DNA
Tumor Suppressor Protein p53