IN-SITU HYBRIDIZATION AND FLOW CYTOMETRIC ANALYSIS OF COLORECTAL TUMORS SUGGESTS 2 ROUTES OF TUMORIGENESIS CHARACTERIZED BY GAIN OF CHROMOSOME-7 OR LOSS OF CHROMOSOME-17 AND CHROMOSOME-18

Chromosomal aberrations in colonic tumourigenesis were investigated by fluorescence in situ hybridization (FISH),vith centromere-specific DN A probes and correlated to pow 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 a berrations were detected in normal colonic epithelium, except for an e xtra chromosome X in one case. In the adenomas, the most frequently oc curring chromosome aberration was a trisomy for chromosome 7, occurrin g 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 carcinom as without endoreduplication, trisomy or tetrasomy for chromosome 7 wa s detected in 12 out of 15 cases (80 per cent). In three of these case s, trisomy 7 was found in combination with loss of chromosome 17 and/o r chromosome 18. In 87 per cent of the carcinomas with endoreduplicati on, 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 carcino mas, 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 ade noma. These results suggest that gain of chromosome 7 is a significant aberration in the tumourigenesis of colonic carcinomas in which no en doreduplication has occurred. No marked clinico-pathological differenc es were observed between tumours of either route of tumourigenesis in this series.