Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers

Suzuki, H., Zhou, X., Yin, J., Lei, J., Jiang, H. Y., Suzuki, Y., Chan, T., Hannon, G. J., Mergner, W. J., Abraham, J. M., Meltzer, S. J. (1995) Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers. Human Molecular Genetics, 4 (10). pp. 1883-1887. ISSN 09646906 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8595411
DOI: 10.1093/hmg/4.10.1883

Abstract

The CDKN2A and CDKN2B genes, encoding p16 and p15 respectively, are located on chromosome 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 (CDK4) and CDK6 and control cellular proliferation by preventing entry into the S phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancer. We previously described CDKN2A exon 2 mutations in a pilot study of 43 esophageal cancers. In order to determine whether CDKN2A and CDKN2B are frequent targets of 9p21 deletion in esophageal carcinogenesis, we have now analyzed 60 primary esophageal cancers for mutations in both exons 1 and 2 of CDKN2A and CDKN2B by direct sequencing of PCR amplified genomic DNAs. In conjunction with our previously published data, we have identified a total of eight nucleic acid substitutions among 60 esophageal carcinomas; here, we describe one new CDKN2B nonsense mutation and one new silent CDKN2B mutation that occurred somatically. Taken together, these results suggest that intragenic mutations in CDKN2A and CDKN2B occur in esophageal cancer, but that they are infrequent events. In view of the known high frequency of loss of heterozygosity at the chromosome 9p21 locus in esophageal cancers, the current data suggest that intragenic mutation is not the predominant mode of inactivation of CDKN2A and CDKN2B or that other genes are targets of deletion at this locus in these cancers.

Item Type: Paper
Uncontrolled Keywords: cyclin dependent kinase article cell cycle s phase cell proliferation chromosome 9p deletion mutant esophagus carcinoma gene mutation heterozygosity human human tissue nucleic acid base substitution polymerase chain reaction priority journal Base Sequence Carrier Proteins Chromosome Deletion Chromosome Mapping Chromosomes, Human, Pair 9 DNA DNA Primers DNA, Neoplasm Enzyme Inhibitors Esophageal Neoplasms Genes, Tumor Suppressor Introns Molecular Sequence Data Pilot Projects Point Mutation Protein p16 Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S.
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
organism description > animal > mammal > primates > hominids > human
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Jessica Koos
Date: 1995
Date Deposited: 12 Aug 2014 15:59
Last Modified: 12 Aug 2014 15:59
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30645

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