Localization of a novel tumor suppressor gene associated with human oral cancer on chromosome 4q25

Recent cytogenetic and molecular studies with highly polymorphic microsatel lite markers have implicated allele loss involving chromosome 4 in several human cancers, which suggests the presence of multiple tumor suppressor gen e (TSG) loci, However, there has been no detailed analysis of loss of heter ozygosity (LOH) on chromosome 4 in oral squamous cell carcinoma (OSCC). To determine the location of a putative TSG associated with OSCC on chromosome 4, polymerase chain reaction (PCR) analysis of microsatellite polymorphism s corresponding to 17 loci was performed to screen 32 patients with OSCC. L OH was observed in the majority of the tumors (75%) in at least one of the loci. The loci on the long arm exhibited a significantly higher frequency o f deletions (66%) than those of the short arm (25%). Among the loci tested, frequent LOH was centered at D4S1573 on 4q25, which represents a region of about 4 centimorgans (cM), However, no commonly deleted regions were found on the short arm of the chromosome, We detected microsatellite instability (MI) in 31% of the cases. MI was also observed more frequently on the long arm (28%) than the short arm (6%), Thus, our data indicate that alteration s of chromosome 4 regions, especially the long arm, are associated with OSC C tumorigenesis and that the 4q25 region may harbor at least one putative T SG.