This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hu, N. Articles by Taylor, P. R. Search for Related Content PubMed PubMed Citation Articles by Hu, N. Articles by Taylor, P. R.

Frequent Inactivation of the TP53 Gene in Esophageal Squamous Cell Carcinoma from a High-Risk Population in China

Divisions of Clinical Sciences [N. H., M. R. B., M. J. R., C. W., S. M. D., P. R. T.] and Cancer Epidemiology and Genetics [A. M. G.], National Cancer Institute, Bethesda, Maryland 20892; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, People’s Republic of China [J. H.]; Shanxi Cancer Hospital and Institute, Taiyuan, Shanxi 030013, People’s Republic of China [Z. Z. T., G. L., W. J. L., Q. H. W., X. Y. H., T. D.]; and Information Management Services, Inc., Silver Spring, Maryland 20904 [C. G.]

Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal cancers worldwide, and north central China has some of the highest rates in the world. Previous studies from tumors in this area of China have shown high frequencies of allelic loss on chromosome 17p13–11, which includes the region where the TP53 gene is found. We examined 56 ESCC patients using single-strand conformation polymorphism and DNA sequencing to assess the frequency and spectrum of TP53 mutation and the association between allelic loss at microsatellite marker TP53 and TP53 mutations. Ninety-six % of cases were found to have at least one genetic alteration, including TP53 mutation (77%), allelic loss within the TP53 gene (73%), and/or loss of heterozygosity at the TP53 microsatellite marker (80%); 75% had two or more such alterations, including 59% with both a point mutation and an intragenic allelic loss ("two hits"). The majority of mutations observed were in exon 5, where the most common type of nucleotide substitution was a G:CA:T or C:GT:A transition, including half that occurred at CpG sites. Allelic loss was most commonly found in exon 4 but was very common in exon 5 as well. Taken together, the multiple genetic alterations of TP53 in this population at high risk for ESCC indicate that there is a very high degree of genetic instability in these tumors, that TP53 is a primary target for inactivation, and that this tumor suppressor gene plays a critical role in the carcinogenesis process for ESCC.

This article has been cited by other articles:

				J.-Y. Chung, T. Braunschweig, N. Hu, M. Roth, J. L. Traicoff, Q.-H. Wang, V. Knezevic, P. R. Taylor, and S. M. Hewitt A multiplex tissue immunoblotting assay for proteomic profiling: a pilot study of the normal to tumor transition of esophageal squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1403 - 1408. [Abstract] [Full Text] [PDF]

				N. Hu, C. Wang, Y. Hu, H. H. Yang, C. Giffen, Z.-Z. Tang, X.-Y. Han, A. M. Goldstein, M. R. Emmert-Buck, K. H. Buetow, et al. Genome-Wide Association Study in Esophageal Cancer Using GeneChip Mapping 10K Array Cancer Res., April 1, 2005; 65(7): 2542 - 2546. [Abstract] [Full Text] [PDF]

				R Naidoo, A Ramburan, A Reddi, and R Chetty Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa J. Clin. Pathol., March 1, 2005; 58(3): 281 - 284. [Abstract] [Full Text] [PDF]

				J. Breton, F. Sichel, A. Abbas, J. Marnay, D. Arsene, and M. Lechevrel Simultaneous use of DGGE and DHPLC to screen TP53 mutations in cancers of the esophagus and cardia from a European high incidence area (Lower Normandy, France) Mutagenesis, May 1, 2003; 18(3): 299 - 306. [Abstract] [Full Text] [PDF]

				H. S. Lo, N. Hu, S. Gere, N. Lu, H. Su, A. M. Goldstein, P. R. Taylor, and M. P. Lee Identification of Somatic Mutations of the RNF6 Gene in Human Esophageal Squamous Cell Carcinoma Cancer Res., August 1, 2002; 62(15): 4191 - 4193. [Abstract] [Full Text] [PDF]

				J. Smeds, P. Berggren, X. Ma, Z. Xu, K. Hemminki, and R. Kumar Genetic status of cell cycle regulators in squamous cell carcinoma of the oesophagus: the CDKN2A (p16INK4a and p14ARF ) and p53 genes are major targets for inactivation Carcinogenesis, April 1, 2002; 23(4): 645 - 655. [Abstract] [Full Text] [PDF]

				N. Hu, G. Li, W.-J. Li, C. Wang, A. M. Goldstein, Z.-Z. Tang, M. J. Roth, S. M. Dawsey, J. Huang, Q.-H. Wang, et al. Infrequent Mutation in the BRCA2 Gene in Esophageal Squamous Cell Carcinoma Clin. Cancer Res., April 1, 2002; 8(4): 1121 - 1126. [Abstract] [Full Text] [PDF]