ALTERATION OF NUMERICAL CHROMOSOMAL-ABERRATIONS DURING PROGRESSION OFCOLORECTAL TUMORS REVEALED BY A COMBINED FLUORESCENCE IN-SITU HYBRIDIZATION AND DNA-PLOIDY ANALYSIS OF INTRATUMORAL HETEROGENEITY

To trace the sequence of numerical chromosomal aberrations during tumo r progression of colorectal tumors, we studied intratumoral heterogene ity of chromosomal copy number by a combined fluorescence in situ hybr idization (FISH) and ploidy analysis. We used six formalin-fixed paraf fin-embedded tumors of which the mucosal lesions were preserved. Nucle ar suspensions were made from the tumor tissues that were scraped from several small regions in 100 mu m thick sections. Copy number of chro mosomes 1, 7, 17, and 18 were examined by FISH with centromeric repeti tive probes. DNA ploidy was monitored by cytofluorometry, and was corr elated to the chromosomal copy number on the smear slides of identical nuclear suspension from each tumor portion. AII the tumors examined i ncluded the DNA-diploid regions in the mucosa, where cancer cells comm only showed monosomy 18 and/or trisomy 7. These chromosomal changes ma y be quite common early events before the occurrence of DNA-aneuploidy in the development of colorectal tumors. Three out of the 6 tumors in cluded near-tetraploid (3.6-4.1C) cells in deeper invasive regions. Ch romosomal constitution of DNA-aneuploid cells was suggested to derive from that of DNA-diploid cells through ploidy duplication with or with out additional loss or gain of chromosomes.