Identification of a Novel Hotspot and a Candidate Tumor Suppressor Gene at 10q21, RHOBTB1, in Head and Neck Cancer

We previously defined human chromosome 10q21 as a hotspot of regional loss in head and neck squamous cell carcinomas (HNSCC) by genome-wide loss of heterozygosity (LOH) analysis. Aims of this study are to narrow-down the target area by using new microsatellite markers and to define candidate tumor suppressor genes (TSG). LOH analysis on 10q21 in 52 HNSCC by 8 highly polymorphic markers indicated distinctive and frequent allelic loss at D10S589 (42%). Among flanking genes, we found the RHOBTB1 gene as a candidate TSG, since an intragenic marker demonstrated the highest LOH (44%). Semi-quantitative expression analysis revealed down-regulation of RHOBTB1 mRNA in 37% of tumors. Interestingly, all tumors that showed decreased expression of RHOBTB1 were accompanied with LOH, supporting the haploinsufficiency and class 2 TSG characteristics of RHOBTB1. Although no pathogenic mutation of RHOBTB1 was found, frequent allelic loss and decreased expression of RHOBTB1 suggested that this gene has a role in tumorigenesis of a subset of HNSCC.