Deletion and mutational inactivation of the cyclin-dependent kinase-4 inhibitor gene (p16) in oral carcinoma

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133404

Law, J C; Ishwad, C; Ferrell, R E ^[1]

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1. Univ. of Pittsburgh, PA (United States); and others

Cyclin dependent kinases (CDKs) are involved in the regulation of cell cycle progression in eukaryotes. G{sub 1}-CDKs act as integrators of growth factor induced signals that initiate the cell cycle in G{sub 1} and commit the cell to enter S phase. The recently identified G{sub 1}-CDK4 inhibitor gene (p16), which maps to chromosome 9p21, has been shown to be deleted or altered in a variety of human tumor cell lines. The p16 gene is thought to act as a tumor suppressor gene by regulating cell cycle progression through the G{sub 1}/S interface. Loss or mutational inactivation of the p16 gene may lead to permutations in the cell cycle which result in an increased susceptibility for tumorigenesis. Sixty-four primary tumors of the oral cavity were analyzed for loss of the p16 gene. Homozygous deletion of the p16 gene was found to occur at a frequency of 8.0% (5/64). An additional 6% of the tumors, without loss of the p16 coding region, showed loss of a sequence tagged site (STS) located in the 5{prime} flanking region of the gene. Additional p16 heterozygous deletions were implied in 6% of the samples (4/64) by loss of heterozygosity for dinucleotide repeat markers for the 9p21 chromosomal region. DNA sequence analysis of exon 2 of the p16 gene, which comprises 70% of the coding region of the gene and has been shown to be frequently mutated in tumor cell lines, was carried out on 48 oral tumors. Mutations were identified in 12% of these samples (6/48), with single base substitutions identified in five samples and a single base insertion identified in the remaining tumor. Our data suggest that deletion and/or mutation of the p16 gene may play a role in the development and progression of oral carcinomas.

• OSTI ID: 133404
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANIMAL CELLS
BIOLOGICAL MARKERS
CARCINOMAS
CELL CYCLE
DNA SEQUENCING
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 9
INHIBITION
PATIENTS
PHOSPHOTRANSFERASES