Abstract: |
Background. Deletion of 9p21 is a common event in many human tumors, including head and neck squamous cell carcinoma (HNSCC). The gene CDKN2, which encodes the protein p16, a cyclin-dependent kinase-4 inhibitor, maps to 9p21. The role of CDKN2 as the tumor suppressor gene in these neoplasms is unclear. The role of loss of heterozygosity (LOH) as a prognostic tool has not been described in HNSCC. Methods. We performed deletion mapping using Southern and PCR-based LOH analysis and prospective survival analysis. Results. We demonstrate that LOH of 9p and, specifically, the interferon (IFN) gene cluster correlates with recurrence of HNSCC. We also demonstrate two separate areas of deletion on 9p, one centromeric to IFNβ and telomeric to CDKN2 and the other centromeric to CDKN2 and telomeric to the polymorphic marker D9S19. All the deletions involve either the markers IFNα and/or D9S171 and D9S126 but not necessarily CDKN2. Conclusions. These results suggest another tumor suppressor gene (TSG) may be involved in HNSCC carcinogenesis and may play a role in aggressive disease as manifest by local, regional, or distant recurrence. |
Keywords: |
adult; clinical article; human tissue; aged; middle aged; survival analysis; gene deletion; carcinoma, squamous cell; recurrent cancer; follow-up studies; prospective studies; polymerase chain reaction; telomere; protein p16; neoplasm recurrence, local; chromosome 9p; chromosomes, human, pair 9; gene product; carcinogenesis; tumor suppressor gene; head and neck cancer; head and neck neoplasms; heterozygosity loss; cyclin-dependent kinase inhibitor p16; loss of heterozygosity; chromosome deletion; cyclin dependent kinase; cyclin dependent kinase inhibitor; polymorphism, genetic; genes, tumor suppressor; head and neck carcinoma; genetic markers; centromere; chromosome map; chromosome mapping; interferon-beta; genes, p16; blotting, southern; interferons; 9p21; humans; prognosis; human; male; female; priority journal; article; ifn
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