Cell cycle regulatory genes are altered frequently in cancer. Such alterations appear to release cell cycle regulatory controls, bypass critical checkpoints and lead to unchecked proliferation. Recent studies have implicated the Cyclin-Dependent Kinase Inhibitor 2 (CDKN2)/ Multiple Tumor Suppressor 1 (MTS1)/p16INK4a gene as a target of frequent inactivation in a wide variety of human tumors. CDKN2 encodes a small polypeptide which inhibits transition beyond the G0/G1 restriction point by inactivating the cyclin D/CDK4 complex, thus appearing to act as a growth suppressor. CDKN2 has been mapped to 9p21, a region exhibiting frequent loss of heterozygosity (LOH) and homozygous deletion in a variety of cancers and cancer-derived cell lines. Such losses may be early events in tumor development We hypothesize that CDKN2 loss is important for the development of oral squamous cell carcinomas (OSCC), and that such losses are early events in tumorigenesis. To examine the timing of CDKN2 aberrations in oral cancer, this study proposes to 1) examine the copy number of CDKN2 by FISH in matched primary OSCC and adjacent oral mucosal specimens compared to normal controls and 2) assess p16 protein expression by immunohistochemistry in paraffin embedded biopsies of the same tissues. These experiments will address important questions regarding tumorigenesis in oral cancer, and potentially allow the development of valuable biomarkers of disease risk, unrecognized early disease and/or prognosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DE005707-02
Application #
2837982
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1998-07-01
Project End
Budget Start
1998-07-01
Budget End
1998-08-07
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Genetics
Type
Schools of Public Health
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Saunders, W S; Shuster, M; Huang, X et al. (2000) Chromosomal instability and cytoskeletal defects in oral cancer cells. Proc Natl Acad Sci U S A 97:303-8
Shuster, M I; Han, L; Le Beau, M M et al. (2000) A consistent pattern of RIN1 rearrangements in oral squamous cell carcinoma cell lines supports a breakage-fusion-bridge cycle model for 11q13 amplification. Genes Chromosomes Cancer 28:153-63