The short arm of chromosome 8 is frequently lost in many human carcinomas including breast cancer, suggesting the presence of a tumor suppressor gene(s) in this region. We identified a gene termed hEXT1L/EXTR1/EXTL3 (hEXT1L hereinafter) that was mapped to chromosome bands 8p12-p21 where frequent LOHs of this region was reported in breast cancer. The existence of the third breast cancer susceptibility gene was also suggested in this region by linkage analysis. We further performed LOH analysis in 8p12-p21 in 34 breast cancers and identified a 5-cM region of common allelic loss that overlapped with the locus for positive lod score in familial breast cancer. We further analyzed genomic alterations of hEXT1L in tumors in which frequent LOHs of 8p were reported. A total of 327 cancers (313 primary tumors and 14 cancer cell lines) including 22 primary breast cancers were analyzed, but none of the tumors had somatic mutations: only one thyroid cancer patient without any family history of cancer had a 9-bp insertion in the constitutional DNA. These results suggest that mutations of hEXT1L do not play a major role in the development of sporadic cancers including breast cancer, and that other tumor suppressor gene(s) exists in the 5-cM region identified in this study.
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