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Breast Cancer in Ataxia Telangiectasia Carriers.
Annual rept. 15 Aug 95-14 Aug 96,
M D ANDERSON CANCER CENTER HOUSTON TX
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This proposal was designed to determine if the ataxia-telangiectasia AT gene acts as a tumor suppressor gene in a subset of breast cancers by looking for tumor loss of constitutional heterozygosity at chromosomal region 1 11q22-q23, the map position of the AT gene. The technical aims were to analyze 300 matched pairs of tumor and normal tissue from breast cancer patients for tumor loss of constitutional heterozygosity using a panel of amplification polymorphisms mapping to 11q22-q23 and, when loss of heterozygosity is detected, to map the extent of that loss. The cloning of the ATM AT, mutated gene reported in June 1995 allows identification of ATM mutations and polymorphisms and consequently allows direct testing of the hypothesis that women who carry these variants of ATM AT carriers are at greater risk for developing breast cancer. During the August 1995 to August 1996 funding period we developed antibodies directed against the ATM gene product and began development of an assay for the detection of AT carriers based on testing RNA isolated from peripheral blood lymphocytes. With the support of the Division of Radiotherapy, we are planning a large, prospective study aimed at determining if AT carrier status increases susceptibility to breast cancer or to normal tissue damage from radiotherapy
APPROVED FOR PUBLIC RELEASE