DNA-REPEAT INSTABILITY IS ASSOCIATED WITH COLORECTAL CANCERS PRESENTING MINIMAL CHROMOSOME REARRANGEMENTS

The DNA-repeat [(CA)n] instability of colorectal cancer cells was stud ied relative to our previously defined classification based on chromos ome alterations. Of the 23 tumors analyzed, 13 belonged to the ''monos omic'' type (MT) characterized by simultaneous loss of chromosome 18 a nd chromosome arm 17p, and many structural rearrangements, 7 to the '' trisomic'' type (TT) with many chromosome gains but few rearrangements , and 3 had a normal karyotype (NT). (CA)n repeat sequences were exami ned on chromosomes 2, 5, 11, 13, 18, and 20. We found sequence alterat ions in 12 tumors at 1 or several loci, 9 of which (1/13 MT, 5/7 TT, a nd 3/3 NT) exhibited a typical shift in allele size defined as microsa tellite instability. Furthermore, a single alteration was observed for the MT tumor, whereas one NT tumor displayed instability on two and a ll the other tumors on three or more loci. These results suggest an in verse relationship between the occurrence of chromosome structural rea rrangements and microsatellite instability, providing another argument for the subdivision of colorectal cancers into groups of distinct onc ogenic pathways. (C) 1995 Wiley-Liss, Inc.