DNA aneuploidy is a
biological marker of the oncogenic potential of colorectal
adenomas. The accumulation of genetic alterations of
cancer-related genes is also essential for colorectal
carcinogenesis. However, it is unclear whether there is any relationship between these genetic alterations and the
DNA ploidy of colon tumour cells in the progression of colorectal
adenomas and early
colorectal carcinomas. Here we have studied the
DNA ploidy state and genetic alterations occurring in colorectal tumours using the crypt isolation technique. Crypts isolated from a total of 106
colorectal tumors (
adenoma, 93; early
carcinoma, 13) were examined using a combination of flow cytometric analysis of
DNA content, polymerase chain reaction-microsatellite assay, and single-strand conformation polymorphism assay for evidence of chromosomal allelic imbalance (AI; 17p; 5q; 18q) or p53 gene mutation. In addition, we examined
microsatellite instability (MSI) with BAT 26 primer sets.
DNA multiploidy was infrequently detected in colorectal
adenomas (15.1%), in contrast to early
carcinomas (46.2%). There was a significant difference in the incidence of AI of chromosome 18q between diploid
adenomas and
aneuploid populations of multiploid
adenomas (18.1% vs 57.1%, p = 0.0043). Mutation of p53 was also found more frequently in
aneuploid populations of early multiploid
colorectal carcinomas than in early diploid
colorectal carcinomas (66.7% vs 0%, p = 0.021). MSI was found in only 2 of 93
adenomas, with no MSI detected in early
colorectal cancers. The two MSI-positive
adenomas were diploid. We subdivided multiploid
adenomas into two groups: those with a low or a high
DNA index (DI). The incidence of genetic alterations of high-DI
adenomas did not differ from those of low-DI
adenomas. Allelic imbalance involving loci on chromosome 18q and mutations of p53 seems to be associated with the progression of diploidy to multiploidy in colorectal tumours. On the other hand, MSI may be associated with the development of some diploid tumours. In addition, the incidence of genetic alterations in the colorectal
adenomas that we examined appears to be independent of the tumour's
DNA index.