SPONTANEOUS CHROMOSOME-ABERRATIONS IN FANCONIS ANEMIA PATIENTS ARE LOCATED AT FRAGILE SITES AND ACUTE MYELOID-LEUKEMIA BREAKPOINTS

Spontaneous chromosome aberrations (CA) were analyzed in 3 Fanconi's a nemia (FA) patients, 8 family members, and 9 healthy individuals. Peri pheral blood lymphocytes obtained from each individual were cultured a nd cytogenetic analysis was performed on standard and sequential G-ban ded metaphases. The numbers of abnormal cells and breaks were found to be higher in AF patients compared to the other groups (p < 0.0001). B reakpoint distribution was statistically analyzed considering the form ula proposed by BROGGER (1977), showing a non-random pattern among FA patients but not among controls os relatives (p < 0.001). Five chromos omal bands located at 1p36, 1p22, 1q21, 3p14, and 3q21 were non-random ly involved in spontaneous CA in FA patients. These bands were correla ted with the chromosomal location of fragile sites, oncogenes, and bre akpoints involved in cancer-rearrangements. A significant correlation with the location of fragile sites (p < 0.03) and breakpoints involved in cancer-rearrangements (p < 0.001), particularly with AML chromosom e anomalies (p < 0.03) was found, suggesting a possible relationship w ith the high predisposition to cancer observed in this disease.