NUMERICAL CHROMOSOME ALTERATIONS IN COLORECTAL CARCINOMAS DETECTED BYFLUORESCENCE IN-SITU HYBRIDIZATION - RELATIONSHIP TO 17P AND 18Q ALLELIC LOSSES

This study concerns DNA ploidy, numerical changes of chromosomes 7, 8, 10, 17 and 18, and allelic losses at chromosomes 17p13.3 (flanking th e p53 gene) and 18q21 (location of the DCC gene) in 31 freshly resecte d colorectal tumours. Cytological smears were used to determine DNA pl oidy by image analysis, and chromosome numbers by fluorescence in situ hybridization (FISH) using chromosome-specific pericentromeric alpha- satellite DNA probes. Allelic losses were assessed by Southern blottin g and by the polymerase chain reaction loss of heterozygosity method. Approximately 50% of the tumours were aneuploid. There was heterogenei ty with respect to chromosome numbers, but gains and losses of chromos omes, or both, were detected in all carcinomas examined, including 10 that were nonaneuploid by image analysis. Trisomy 7 was found in 74% o f the tumours, and monosomy of chromosome 18 in 32%. Allelic loss at c hromosome 17p13.3 was evident in 13 of 26 informative cases, and only one case exhibited monosomy 17. In comparison monosomy 18 was found in 10 cases; 7 of them corresponded to approximately half of the cases w ith allelic loss within the DCC gene, and the other three were noninfo rmative. These findings indicate that the loss of one chromosome 18 is an important mechanism producing allelic deletion of the DCC gene in colorectal carcinomas. Our data also suggest that monosomy 18 is a use ful indicator for studying colorectal cancer progression on a cell by cell basis.