Characterization of Early Genomic Changes in Mammary Glands in High Risk Women

Abstract : Because many of the familial breast cancer patients carry a mutation in BRCAl on chromosome l7 or BRCA2 on chromosome 13, the first genetic event that may occur in their mammary glands to begin the progression toward cancer may be loss of heterozygosity (LOH) on one of these two chromosomes. it is unknown if these genetic changes correspond to a recognizable histopathological abnormality. We hypothesize that such genomic changes may precede morphologic changes and thus we may detect evidence for such changes in morphologically normal breast tissues or benign lesions surrounding breast tumors in BRCAl/2 positive patients. We have recently developed a panel of 15 markers to study LOH in morphologically well characterized and carefully laser capture microdissected, breast tissues from a group of BRCAl/2 positive patients with breast cancer who are followed up by our Cancer Genetics Program at the Lombardi Cancer Center. Our studies so far support our hypothesis. Specifically, we performed a total of 105 analyses at different loci using microdissected breast tissues for areas showing normal morphology or benign changes surrounding the tumor tissues in BRCA carriers with breast cancer. Overall, LOH was detected in 59 studies (56%) . In the normal tissues, 15 of 30 analyses (50%) showed LOH and in the tissues with proliferative changes 44 of %5 analyses showed LOH (59%)