The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma
Open accessAbstract
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. Significance: This is the first genome-wide study of mutations in esophageal cancer. It identifies key genetic differences between EACs and ESCCs including general mutation spectra and NOTCH1 loss-of-function mutations specific to ESCCs, shows geographic disparities between North American and Chinese ESCCs, and shows that most mutations in EACs are already present in matched Barrett esophagus. Cancer Discov; 2(10); 899–905. ©2012 AACR. Read the Commentary on this article by Collisson and Cho, p. 870. This article is highlighted in the In This Issue feature, p. 857.
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Cited by
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863
Self-citationNotch signaling pathway: architecture, disease, and therapeutics
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Identification of genomic alterations in oesophageal squamous cell cancer
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Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974
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Metadata
- Authors
- Agrawal, N., Jiao, Y., Bettegowda, C., Hutfless, S. M., Wang, Y., David, S., Cheng, Y., Twaddell, W. S., Latt, N. L., Shin, E. J., Wang, L.-D., Wang, L., Yang, W., Velculescu, V. E., Vogelstein, B., Papadopoulos, N., Kinzler, K. W., & Meltzer, S. J.
- Venue
- Cancer Discovery
- Published
- 2012-10-01
- Volume
- 2
- Issue
- 10
- Pages
- 899-905
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2114715773
- Cited by
- 381
- References
- 53
- FWCI
- 32.47
- Type
- journal article
- Language
- en
- Open access
- green
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- Agrawal, N., Jiao, Y., Bettegowda, C., Hutfless, S. M., Wang, Y., David, S., Cheng, Y., Twaddell, W. S., Latt, N. L., Shin, E. J., Wang, L.-D., Wang, L., Yang, W., Velculescu, V. E., Vogelstein, B., Papadopoulos, N., Kinzler, K. W., & Meltzer, S. J. (2012). Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-12-0189
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