title: In situ hybridization and flow cytometric analysis of colorectal tumours suggests two routes of tumourigenesis characterized by gain of chromosome 7 or loss of chromosomes 17 and 18.
abstract: Chromosomal aberrations in colonic tumourigenesis were investigated by fluorescence in situ hybridization (FISH) with centromere-specific DNA probes and correlated to flow cytometry (FCM) results in a series of tissues including normal colonic epithelium, adenomas, and carcinomas, as well as adenomas adjacent to carcinomas. No numerical chromosome aberrations were detected in normal colonic epithelium, except for an extra chromosome X in one case. In the adenomas, the most frequently occurring chromosome aberration was a trisomy for chromosome 7, occurring in 37 per cent of the cases. In the carcinomas, two distinct routes of genetic aberration could be established on the basis of correlation with FCM: one with and one without endoreduplication. In the carcinomas without endoreduplication, trisomy or tetrasomy for chromosome 7 was detected in 12 out of 15 cases (80 per cent). In three of these cases, trisomy 7 was found in combination with loss of chromosome 17 and/or chromosome 18. In 87 per cent of the carcinomas with endoreduplication, loss of chromosome 17 and/or 18 was found, while in only one case was gain of chromosome 7 detected. In the adenomas adjacent to carcinomas, trisomy 7 was found in 36 per cent of the cases. In these cases, the concomitant adenocarcinomas showed the same numerical chromosome 7 aberration, plus extra aberrations for other chromosomes. In only two cases the carcinoma demonstrated trisomy 7 with a normal adjacent adenoma. These results suggest that gain of chromosome 7 is a significant aberration in the tumourigenesis of colonic carcinomas in which no endoreduplication has occurred. No marked clinico-pathological differences were observed between tumours of either route of tumourigenesis in this series.
authors.affiliation: Department of Pathology, University Hospital Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Herbergs
authors.forename: A H
authors.initials: AH
authors.lastname: Hopman
authors.forename: A P
authors.initials: AP
authors.lastname: De Bruïne
authors.forename: F C
authors.initials: FC
authors.lastname: Ramaekers
authors.forename: J W
authors.initials: JW
authors.lastname: Arends
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000236:Adenoma / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002897:Chromosomes, Human, Pair 7; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D014314:Trisomy