Frequent Deletion and Down-Regulation of ING3 in Head and Neck Cancer

Loss of heterozygosity (LOH) has been frequently detected at chromosome 7q31 region in human head and neck squamous cell carcinomas (HNSCC) and many other cancers, suggesting the existence of the tumor suppressor genes (TSG). However, the targeted gene was yet identified. We analyzed LOH at 7q31 region in 49 HNSCC by using 6 polymorphic microsatellite markers and found allelic deletion in 48% of the informative cases. We detected two preferentially deleted locations one around D7S643 and the other around D7S486. When we redefined the map of 7q31 region according to the contiguous sequences, an ING1 like gene, ING3, which we named it due to homology to ING1, was found in the proximity of D7S643. ING3 protein harbors a PHD zinc finger domain highly homologous among ING family proteins, in which we previously found mutations in a related gene, ING1. As only one missense mutation of the ING3 gene was found in HNSCC, we examined the mRNA expression levels. RT-PCR analysis demonstrated decreased or no expression of ING3 mRNA in 45 % of primary tumors as compared with that of mathced normal samples. All these findings suggest a possibility that ING3 functions as a TSG in a subset of HNSCC.