Genetic alterations in DNA diploid, aneuploid and multiploid colorectal carcinomas identified by the crypt isolation technique

Loss of heterozygosity (LOH) and microsatellite instability (MSI) commonly occur in colorectal carcinomas, However, the role of these genetic alterati ons in determining DNA ploidy status of tumors (diploid, aneuploid and mult iploid) remains unclear. In the present study, we attempted to clarify the relationship between genetic alterations and DNA ploidy status. Crypt isola tion coupled with DNA cytometric sorting and polymerase chain reaction assa y(17 microsatellite markers) were used to study allelic losses and MSI in 5 9 colorectal carcinomas (diploid, 15; aneuploid, 10 and multiploid, 34), Of the 15 diploid carcinomas, 6 exhibited MSI in which allelic losses were ra rely found, The other 9 diploid tumors mostly exhibited allelic losses, but none displayed MSI status. Whereas allelic losses frequently occurred in t he aneuploid carcinomas and the aneuploid populations of multiploid carcino mas, they were rarely detected in the diploid populations of multiploid car cinomas. MSI status was not observed in aneuploid carcinomas nor in either population of multiploid carcinomas. Although multiploid carcinomas genetic ally resemble aneuploid carcinomas in the expression of the severe LOH phen otype, the genetic alterations seen in the diploid populations of multiploi d carcinomas may differ from those of diploid carcinomas. Furthermore, all diploid, aneuploid and both the diploid and aneuploid fractions of the mult iploid rumors that were non-MSI exhibited a high rate of LOH, suggesting th at LOH is independent of the tumor's ploidy status. (C) 2000 Wiley-Liss, In c.