High Loss of Heterozygosity of 9p24 Region and Identification of BRM as A Candidate Tumor Suppressor Gene in Head and Neck Cancer

Abstract

Biochemical and genetic studies has identified several ATP-dependent multiprotein complexes that are involved in the remodeling of chromatin during gene activation. The SWI/SNF complex is one of these molecules. Molecular pathological changes of several members of SWI/SNF complex, especially human brahma (hBRM) and brahma-related gene 1 (BRG1) were reported to be involved in carcinogenesis of human cancer. hBRM can bind and cooperate with hypophosphorylated RB protein in repressing E2F1 transcriptional activation in transient transfection studies. We analyzed the LOH of the short arm of chromosome 9 in 64 head and neck squamous cell carcinomas by using 13 highly polymorphic microsatellite markers and found two deletion hot spots at 9p21 and 9p24. P16 tumor suppressor gene is likely to be a target for the deletion of 9p21 region. When the map of 9p24 region was redefined, a possible tumor suppressor gene hBRM was identified. Therefore we prepared an hBRM specific microsatellite marker and found 67% deletion of this gene at 9p24 region. In RT-PCR analysis about 60% of tumor samples demonstrated reduced mRNA expression as compared to matched normal samples.