CHROMOSOME DIVISION FIGURES REVEAL GENOMIC INSTABILITY IN TUMORIGENESIS OF HUMAN COLON MUCOSA

A variety of chromosomal gains and losses has been detected with compa rative genomic hybridization during tumorigenesis in the colon mucosa. The aim of this investigation was to corroborate increasing genomic i nstability and to elucidate those lesions in which the record from com parative genomic hybridization has remained unexpectedly negative. Rep licate paraffin-embedded samples were investigated in detail using ima ge microphotometry. crucial to the recent approach was the fact that t he histological compartments were exactly matched and that the single- cell measurements were highly accurate (GV at 0.05). Feulgen DNA was q uantified in interphase nuclei and chromosome division figures, which were found in all cases of high-grade dysplasia and, with increased fr equency, of colon carcinoma. The genomic imbalance in chromosome divis ion figures was quantified by the sensitive 4.5 c exceeding rate (wher e c is the haploid genome equivalent), which was also positive in case s with a negative record from comparative genomic hybridization. The D NA content of chromosome division figures was measured with a mean 4.5 c exceeding rate of 25.8 +/- 4.4% standard error in 12 cases of high- grade dysplasia and of 62.1 +/- 7.1% in colon carcinoma (16 cases). Th e chromosome division figures were considered to be the first morpholo gical manifestation of genomic instability attending precancerous cond itions in the colon. Telophase-like chromosome division figures with u nequal amounts of DNA in their hemispheres revealed gross somatic muta tions before clonal selection.