Mapping of the candidate tumor suppressor genes’ loci on human chromosome 3 in head and neck squamous cell carcinoma of an Indian patient population

Abstract 

The candidate tumor suppressor genes’ (TSG) loci on human chromosome 3 (chr.3) were mapped in six dysplastic lesions and 51 primary squamous cell carcinoma from head and neck region of an Indian patient population by using 20 highly polymorphic microsatellite markers. The two chromosomal regions 3p12-13 and 3p21.2-22 have shown the highest losses of heterozygosity (LOHs) of 34.6–38% and 37–46%, respectively with statistically significant clinical correlation’s with tobacco habit, positive lymph node and tumor stages. In addition, high frequencies of microsatellite size alterations (MAs) of 16.2–28.5% and 23.8–28.2% were observed in the chromosomal 3p11-13 and 3p21.2-22 regions, respectively, with significant above-mentioned clinical correlation only in the 3p11-13 region. In the dysplastic lesions, the prevalence of LOHs compared to the MAs had indicated that LOHs might be the early events. Five tumors at stage-III/IV seemed to have lost an entire normal copy of chr.3. It was of particular note that 17% (10/57) of the samples showed rare bi-allelic alterations mainly in and around the high LOHs regions. Thus, (1) the gradual increase of LOHs/MAs during progression of the tumor, (2) high frequencies of MAs, (3) rare bi-allelic alterations in and around high LOHs regions and (4) loss of wild type chr.3 in the later stages of tumor development have suggested that such alterations might provide selective growth advantage to the tumors. Also, we propose from our data that the high LOHs regions (3p12-13 and 3p21.2-22) could harbour putative TSG(s), responsible for the development of head and neck squamous cell carcinoma.

Keywords:  Head and neck squamous cell carcinoma, Chromosome 3, Tumor suppressor gene (s), Loss of heterozygosity, Microsatellite size alteration