Abstract
Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. We therefore performed comprehensive analyses on loss of heterozygosity (LOH) using a genome-wide panel of 191 microsatellite markers in 22 HNSCC samples. We found 53 markers with significantly high LOH (>30%) on 21 chromosomal arms; the highest values of those were observed on 3p, 9p, 13q, 15q, and 17p, corresponding to D3S2432 (67%), D9S921-D9S925 (67%) and GATA62F03 (86%), D13S1493 (60%), D15S211 (62%), and D17S1353 (88%), respectively. Fifteen hot spots of LOH were defined in 13 chromosomal arms: 2q22-23, 4p15.2, 4q24-25, 5q31, 8p23, 9p23-24, 9q31.3, 9q34.2, 10q21, 11q21-22.3, 14q11-13, 14q22.3, 17p13, 18q11, and 19q12 as loci reported previously in HNSCCs. Furthermore, we identified five novel hot spots of LOH on three chromosomal arms in HNSCC at 2q33 (D2S1384), 2q37 (D2S125), 8q12-13 (D8S1136), 8q24 (D8S1128), and 15q21 (D15S211). In conclusion, our comprehensive allelotype analyses have unveiled and confirmed a total of 20 possible TSG loci that could be involved in the development of HNSCC. These results provide useful clues for identification of putative TSGs involved in HNSCC by fine mapping of the suspected regions and subsequent analysis for functional genes.
Highlights
Chromosomal arms 3p, 9p, 13q, 15q, and 17p showed loss of heterozygosity (LOH) frequencies of higher than 40%, whereas the LOH frequencies of 2q, 3q, 4p, 4q, 5q, 8p, 8q, 9q, 10q, 11p, 11q and 14q were more than 20%
3p and 15q seemed to have total deletion of each chromosomal arm in four and five tumor samples, respectively, which made it difficult to focus on the target area carrying putative tumor suppressor gene (TSG)
With respect to the 15q arm, we found a significantly high frequency of LOH at D15S211 (62%), the entire 15q arm seemed to be lost in approximately 25% of Head and neck squamous cell carcinoma (HNSCC) specimens
Summary
Our study is the most comprehensive genomic study of HNSCCs to date, covering all of the nonacrocentric chromosome arms with 191 microsatellite markers, most of which are different from those used previously.
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