Assessments of clonal composition of colorectal adenomas by fish analysis of chromosomes 1, 7, 13 and 20

Chromosome banding analysis has shown that numerical aberrations, in partic ular gains of chromosomes 7, 13 and 20, are common in colorectal adenomas b ut cannot provide reliable information on the size of the abnormal clones i n vivo. We examined interphase nuclei from 70 colorectal adenomas, of which 64 had been previously karyotyped, using fluorescence in situ hybridizatio n (FISH) with probes for the pericentromeric regions of chromosomes 1, 7, 1 3 and 20, Cain of chromosome 7 was seen in 34% of the analyzed adenomas, +1 3 was seen in 44% and trisomy 20 was found in 32% of the adenomas, verifyin g that the trisomies are in vivo phenomena. The median proportion of cells with trisomy was larger than 50%. A comparison with the C-banding analysis showed a good correlation between the results yielded by the 2 methods, Bas ed on the clonal size and karyotypic findings, a likely order of events dur ing clonal evolution could be ascribed to each case. More than I numerical aberration was detected by FISH analysis in 16 adenomas, In 6 adenomas, a c lone with only trisomy 7 was present alongside a clone with additional gain (s) of chromosomes 13 and/or 20, Seven cases had gain of chromosome 13 and/ or gain of chromosome 20 in the largest clone, suggesting that a clone with either of these changes was present before the changes in chromosome 7 cop y number took place. On the basis of the results of this combined meta- and interphase cytogenetic study, we conclude that gains of chromosomes 7, 13 and 20 are common in colorectal adenomas and that the trisomies usually are present in a large proportion of the cells. They seem to be primary chromo some aberrations in some adenomas, whereas in others they arise secondarily as part of the clonal evolution. Although the first gain usually is of chr omosome 7, it is evident that it is the end result of the chromosomal aberr ations, not the exact sequence in which they occur, that determines the pat hogenetic consequences. (C) 2000 Wiley-Liss. Inc.