Abstract
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 tumor suppressor genes (TSG). We analysed LOH at 7q31 region in 49 HNSCC by using six polymorphic microsatellite markers and found allelic deletion in 48% (22/46) of the informative cases. We detected two preferentially deleted regions, one is around D7S643 and the other around D7S486. When we redefined the map of 7q31 region according to the contiguous sequences, a recently identified gene, ING3, was found in the proximity of D7S643. ING3 protein harbors the PHD 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 expression level. Reverse-transcription-PCR analysis demonstrated decreased or no expression of ING3 mRNA in 50% of primary tumors as compared with that of matched normal samples. Especially, about 63% of tongue and larynx tumors showed the decrease and a tendency of higher mortality was observed in cases with decreased ING3 expression. All these findings suggest a possibility that the ING3 gene functions as a TSG in a subset of HNSCC.
Highlights
Tumor suppressor genes (TSG) are de®ned as genetic elements whose loss or mutational inactiva-Loss of heterozygosity (LOH) analysis by using polymorphic microsatellite markers is a sensitive method to detect micro-deletions
We examined LOH using six microsatellite markers on the chromosome 7q22-31 region in 49 paired normal and head and neck squamous cell carcinomas (HNSCC) DNAs
Markers D7S643 and D7S486 showed the highest incidence of LOH with a
Summary
Tumor suppressor genes (TSG) are de®ned as genetic elements whose loss or mutational inactiva-Loss of heterozygosity (LOH) analysis by using polymorphic microsatellite markers is a sensitive method to detect micro-deletions. Recent studies have shown the frequent LOH at chromosomal region 7q31 in HNSCC (Zenklusen et al, 1995; Wang et al, 1998), and in various types of human cancers including breast, prostate, colon, ovary, thyroid and renal cell carcinomas (Latil et al, 1995; Takahashi et al, 1995; Zenklusen et al, 1995; Lin et al, 1996; Shridhar et al, 1997; Bieche et al, 1997; Zhang et al, 1998; Edelson et al, 1997). We examined the 7q22-31 region by using a set of highly polymorphic microsatellite markers to ®nd out allelic loss in HNSCC. The prototype of the ING family gene, ING1, has been inferred for possible TSG function (Garkavtsev et al, 1996) and we have recently found allelic loss and tumor-speci®c mutations of the gene in HNSCC (Gunduz et al, 2000)
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