Non-random distribution of spontaneous chromosome aberrations in two Bloom Syndrome patients

The distribution of breakpoints involved in spontaneous chromosome aberrations (CA) was analyzed in lymphocytes from a family with Bloom's Syndrome (BS) and 9 healthy individuals. Standard and G-banded metaphases from each individual were analyzed to allow the identification of the breakpoints involved in spontaneously occurring chromosome aberrations. A total of 85 breakpoints in BS patients, 17 in their parents and 35 in controls, could be exactly localized to specific chromosome bands. Breakpoint distribution was statistically analyzed considering the formula proposed by Brøgger (1977), showing a non-random pattern in BS patients. Thirteen bands non-randomly involved in spontaneous CA (p < 0.005) were recognized in BS, located at 1p36, 1q21, 1q32, 2q33, 3p24, 3p14, 3q27, 5q31, 6p21, 7q22, 9q13, 11q13, and 17q23. Only 1 band (1q21) was significantly implicated in both parents (p < 0.005), while controls showed a random distribution. BS non-random bands were correlated with the chromosomal location of fragile sites, oncogenes, and breakpoints involved in cancer rearrangements. A significant correlation with the location of fragile sites and cancer-breakpoints (p < 0.005), particularly with acute myeloid leukemia and malignant lymphomas rearrangements was found. These findings demonstrate that constitutional chromosome instability in BS might involve specific points, such as fragile sites and cancer breakpoints, suggesting an association with the increased incidence of cancer.