Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in thislocus

The short arm of chromosome 8 is frequently lost in many human carcinomas i ncluding breast cancer, suggesting the presence of a tumor suppressor gene( s) in this region. We identified a gene termed hEXT1L/EXTR1/EXTL3 (hEXT1L h ereinafter) that was mapped to chromosome bands 8p12-p21 where frequent LOH s of this region was reported in breast cancer. The existence of the third breast cancer susceptibility gene was also suggested in this region by link age analysis. We further performed LOH analysis in 8p12-p21 in 34 breast ca ncers and identified a 5-cM region of common allelic loss that overlapped w ith 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 a ny 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 i n the development of sporadic cancers including breast cancer, and that oth er tumor suppressor gene(s) exists in the 5-cM region identified in this st udy.