Evaluation of myc and chromosome 8 copy number in colorectal cancer using interphase cytogenetics.

Abstract

To reveal the significance of genetic abnormalities of the c-myc gene, 56 colorectal tumors (43 colorectal carcinomas, 5 recurrent or metastatic tumors, and 8 adenomatous polyps) were analyzed using fluorescence in situ hybridization (FISH). Two probes specific for c-myc and the chromosome 8 centromere were used for dual color FISH. In each case, 100-200 nuclei were observed for signals from the probes. The percent of nuclei with c-myc amplification (PMA) was defined as the proportion of nuclei representing the ratio of c-myc/chromosome 8 >1.0, and the percent of nuclei with the greater number of c-myc (PGNM) was defined as the proportion of nuclei representing the ratio of c-myc/chromosome 8 > or =2.0. Low level amplification was defined as a case with PMA > or =10% and PGNM <10%. High level amplification was defined as a case with PGNM > or =10%. While adenomatous polyps and in situ carcinomas showed no c-myc amplification, the low level amplification and high level amplification of c-myc were observed in 48.8% (21/43) and 20.9% (9/43) of primary colorectal carcinomas. In addition, the group including cases of stage IIIb and IV exhibited significantly higher average copy numbers of c-myc (CN-myc), PMA and PGNM than the other group of earlier stages. FISH was thought a useful cytogenetic method to detect genetic abnormalities in solid tumors. It was shown that the c-myc gene amplification identified using FISH was associated with the aggressiveness of colorectal carcinoma.