Objective: Loss of heterozygosity (LOH) studies indicate that allelic loss associated with the development of head and neck of squamous cell carcinoma occurs most frequently at 9p21-22. However, the target of chromosome 9p21-22 loss has been the source of significant debate. A putative tumor suppressor gene, p16, has been identified at the 9p21 location, but genetic alterations of p16 located in this region are unusual. To refine the hot spots of LOH on chromosome 9p13-23 will be helpful to find other putative tumor suppressor genes in laryngeal squamous cell carcinoma.
Methods: The sections of paraffin-embedded tumor tissues were microdissected to enrich for neoplastic cells. LOH on 9p13-23 was analyzed in a set of 42 paired blood and tumor samples using polymerase chain reaction (PCR) with 13 highly polymorphic microsatellite markers.
Results: Of the 42 total tumors, 41(97.6%) showed LOH in at least one of the microsatellite markers tested at the chromosome 9p13-23 region. The most frequently deleted marker was D9S162 with in 17 of 19 (89.5%) informative samples. The marker D9S171, which is located in 9p21, had LOH detected in 12 of 15 informative cases (80.0%). LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of 36 informative cases (50.0%). Fine deletion mapping also revealed two minimal regions of LOH encompassing markers D9S161-D9S171 at 9p21 and IFNA-D9S162 at 9p22-23.
Conclusion: These findings imply the high frequency of LOH at 9p13-23 in laryngeal squamous cell carcinoma and the presence of at least two as yet unidentified tumor suppressor genes in 9p13-23 region. Those putative tumor suppressor genes may become inactivated during the progression of the laryngeal squamous cell carcinoma.