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Detection and Cloning of a Common Region of Loss of Heterozygosity at Chromosome 1p in Breast Cancer¹

Jefferson Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107

The short arm of chromosome 1 is frequently affected by rearrangements in a variety of human malignancies. Genetic alterations, predominantly deletions, which are indicative of the presence of a putative tumor suppressor gene at chromosome 1p, are observed in breast cancer. In order to define the altered locus, eleven highly polymorphic microsatellite markers on chromosome 1p were used to detect loss of heterozygosity. We analyzed 52 cases of breast cancer and found 4 common deleted regions at chromosome 1p. Twenty-two of 52 (42%) informative patients showed at least 1 affected locus. The region most frequently exhibiting loss of heterozygosity was 1p31 (11/39; 28%); the other three common deleted 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 suppressor genes may reside on chromosome 1p. We have cloned the entire region of interest at 1p31 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.

¹ This work was supported by a National Cancer Institute Outstanding Investigator Grant CA39860 (to C. M. C.).

² To whom requests for reprints should be addressed, at Thomas Jefferson University, Jefferson Medical College, 233 South 10th St., BLSB, Room 1050, Philadelphia, PA 19107-5799.

Received 1/19/95. Accepted 3/ 1/95.

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