DETECTION AND CLONING OF A COMMON REGION OF LOSS OF HETEROZYGOSITY ATCHROMOSOME 1P IN BREAST-CANCER

The short arm of chromosome 1 is frequently affected by rearrangements in a variety of human malignancies. Genetic alterations, predominantl y deletions, which are indicative of the presence of a putative tumor suppressor gene at chromosome 1p, are observed in breast cancer. In or der to define the altered locus, eleven highly polymorphic microsatell ite markers on chromosome 1p were used to detect loss of heterozygosit y. We analyzed 52 cases of breast cancer and found 4 common deleted re gions at chromosome 1p. Twenty-two of 52 (42%) informative patients sh owed at least 1 affected locus. The region most frequently exhibiting loss of heterozygosity was 1p31 (11/39; 28%); the other three common d eleted regions were 1p36 (10/44; 23%), 1p35-36 (5/40; 13%), and 1p13 ( 8/39; 21%). These data suggest that one or more putative tumor suppres sor genes may reside on chromosome 1p. We have cloned the entire regio n of interest at 1p31 in yeast artificial chromosomes. This yeast arti ficial chromosome contig can be used for fine mapping of the region an d cloning of the candidate tumor suppressor gene.