Constitutional alterations of 9p23-24 in independent BRCA2 breast cancer families

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Germ line mutations of BRCA2 are predicted to account for the majority of families with both male and female breast cancer. However, there is circumstantial evidence that the cancer risk conferred by BRCA2 mutation may be modified by other genetic or environmental factors. By employing a combination of classical G-banding and fluorescence in situ hybridization analyses we have identified chromosomal alterations on 9p23-24 in peripheral lymphocytes of independent BRCA2 breast cancer patients. Tandem duplication and amplification with inversion are constitutional rearrangements in four male breast cancer patients from two high-risk families. Interstitial deletion of the same region was found in four male and one female patients from an independent family. The biological significance of the coexistence of BRCA2 mutation and 9p23-24 abnormalities in breast cancer families may be complex. Possible explanations include (1) the BRCA2 mutation is related to the 9p-rearrangement, or (2) the 9p rearrangement is elicited by another as yet unknown factor, and chromosomal changes on 9p could be related to modifying cancer risk.