Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes

Comparative genomic hybridization (CGH) is used to detect amplified and/or deleted chromosomal regions in tumours by mapping their locations on normal metaphase chromosomes. Forty-five sporadic colorectal carcinomas were scre ened for chromosomal aberrations using direct CGH. The median number of chr omosomal aberrations per tumour was 7.0 (range 0-19). Gains of 20q (67%) an d losses of 18q (49%) were the most frequent aberrations. Other recurrent g ains of 5p, 6p, 7, 8q, 13q, 17q, 19, X and losses of 1p, 3p, 4, 5q, 6q, 8p, 9p, 10, 15q, 17p were found in > 10% of colorectal tumours. High-level gai ns (ratio > 1.5) were seen only on 8q, 13q, 20 and X, and only in DNA aneup loid tumours. DNA aneuploid tumours had significantly more chromosomal aber rations (median number per tumour of 9.0) compared to diploid tumours (medi an of 1.0) (P < 0.0001). The median numbers of aberrations seen in DNA hype rdiploid and highly aneuploid tumours were not significantly different (8.5 and 11.0 respectively; P = 0.58). Four tumours had no detectable chromosom al aberrations and these were DNA diploid. A higher percentage of tumours f rom male patients showed Xq gain and 18q loss compared to tumours from fema le patients (P = 0.05 and 0.01 respectively). High tumour S phase fractions were associated with gain of 20q13 (P = 0.03), and low tumour apoptotic in dices were associated with loss of 4q (P = 0.05). Tumours with TP53 mutatio ns had more aberrations (median of 9.0 per tumour) compared to those withou t (median of 2.0) (P = 0.002), and gain of 8q23-24 and loss of 18qcen-21 we re significantly associated with TP53 mutations (P = 0.04 and 0.02 respecti vely). Dukes' C/D stage tumours tended to have a higher number of aberratio ns per tumour (median of 10.0) compared to Dukes' B tumours (median of 3.0) (P = 0.06). The low number of aberrations observed in DNA diploid tumours compared to aneuploid tumours suggests that genomic instability and possibl e growth advantages in diploid tumours do not result from acquisition of gr oss chromosomal aberrations but rather from selection for other types of mu tations. Our study is consistent with the idea that these two groups of tum ours evolve along separate genetic pathways and that gross genomic instabil ity is associated with TP53 gene aberrations.