Heterozygosity at Chromosome 1 p in Breast Cancer Detection and Cloning of a Common Region of Loss of Updated

The short arm of chromosome 1 is frequently affected by rearrange ments in a variety of human malignancies. Genetic alterations, predomi nantly deletions, which are indicative of the presence of a putative tumor suppressor gene at chromosome Ip, are observed in breast cancer. In order to define the altered locus, eleven highly polymorphic microsatellite markers on chromosome Ip were used to detect loss of heterozygosity. We analyzed 52 cases of breast cancer and found 4 common deleted regions at chromosome Ip. Twenty-two of 52 (42%) informative patients showed at least 1 affected locus. The region most frequently exhibiting loss of het erozygosity was Ip31 (11/39; 28%); the other three common deleted regions were Ip36 (10/44; 23%), lp35-36 (5/40; 13%), and Ipl3 (8/39; 21%). These data suggest that one or more putative tumor suppressor genes may reside on chromosome Ip. We have cloned the entire region of interest at Ip31 in yeast artificial chromosomes. This yeast artificial chromosome contig can be used for fine mapping of the region and cloning of the candidate tumor suppressor gene.

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