Intratumor heterogeneity of chromosome 1, 7, 17, and 18 aneusomies obtained by FISH and association with flow cytometric DNA index in human colorectal adenocarcinomas

Background: The origin and evolution of somatic chromosome aberrations in c olorectal cancer is still poorly understood. The data in the literature sug gest that some specific chromosome aberrations are more common. It is not k nown, however, if there is a correlation of these with near-diploid and hig h aneuploidy previously proposed to be a characteristic of the adenoma-carc inoma sequence. Methods: Chromosome 1, 7, 17 and 18 numerical aberrations and Ip deletions were evaluated by fluorescence in situ hybridization analysis for 20 human sporadic colorectal adenocarcinomas in 70 distinct tumor sectors and correl ated with flow cytometric DNA index (DI) values. Results: Aneusomy for at least one of the investigated chromosomes was obse rved in 60 of 70 tumor sectors corresponding to 19 of 20 adenocarcinomas (9 5%) Deletions at 1p, observed in 8 of 18 adenocarcinomas (44%), were intrat umor homogeneous in 7 of 8 tumors. In contrast, the other aberrations were intratumor heterogeneous. Aneusomies of chromosomes 1, 7, and 17 were stron gly associated with DNA high aneuploidy (DI greater than or equal to 1.4), whereas aneusomy of chromosome 18 and 1p deletions were equally common amon g DNA diploid and near-diploid tumors (DI < 1.4 and DI not equal 1). Conclusions: Overall, these data suggest the existence of different aneuplo idization routes correlated with specific chromosome aberrations. In additi on, intratumor homogeneity of Ip deletions appears to be an indication of e arly occurrence or strong selection. We also suggest that tumors with monos omies and in particular monosomies-trisomies for the same chromosomes suppo rt a model of aneuploidization and chromosome instability during the colore ctal tumor progression based on loss of symmetry during chromosome segregat ion (Giaretti: Lab Invest 71:904-910, 1994). (C) 1999 Wiley-Liss, Inc.