Heterogeneity studies identify a subset of sporadic colorectal cancers without evidence for chromosomal or microsatellite instability
- 23 December 1999
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 18 (56), 7933-7940
- https://doi.org/10.1038/sj.onc.1203368
Abstract
Two apparently independent mechanisms of instability are recognized in colorectal cancer, microsatellite instability and chromosomal instability. Evidence from colorectal cancer cell lines indicates the presence of either, or both, types of instability in the vast majority. Here, we sought to determine the prevalence of such instability in primary sporadic colorectal cancers. Microsatellite instability was established by demonstration of ovel clonal, nongerm-line alleles in at least two of four tested loci. Chromosomal abnormalities were identified by comparative genomic hybridization (CGH) and flow cytometric analysis of nuclear DNA content. Tumours harbouring chromosomal instability were distinguished from those with stable but aneuploid karyotypes by comparing chromosomal defects at multiple sites throughout each cancer. This analysis allowed assessment of both the number of chromosomal abnormalities and their heterogeneity throughout the tumour. The results confirm that microsatellite instability is consistently associated with multiple, repeated changes in microsatellites throughout the growth of the affected colorectal carcinomas. There were also several carcinomas in which major structural or numerical abnormalities in chromosomes had clearly continued to arise during tumour growth. However, a substantial subset of tumours showed neither microsatellite instability nor multiple, major chromosomal abnormalities. We suggest that the development of a proportion of colorectal cancers proceeds via a different pathway of carcinogenesis not associated with either of the currently recognized forms of genomic instability.Keywords
This publication has 26 references indexed in Scilit:
- Chromosome number and structure both are markedly stable in RER colorectal cancers and are not destabilized by mutation of p53Oncogene, 1998
- Mutations of mitotic checkpoint genes in human cancersNature, 1998
- Mismatch repair defects in human carcinogenesisHuman Molecular Genetics, 1996
- Mutation of the p53 gene precedes aneuploid clonal divergence in colorectal carcinomaBritish Journal of Cancer, 1995
- The 1993–94 Généthon human genetic linkage mapNature Genetics, 1994
- Mutation in the DNA mismatch repair gene homologue hMLH 1 is associated with hereditary non-polyposis colon cancerNature, 1994
- Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesisNature, 1993
- Clues to the Pathogenesis of Familial Colorectal CancerScience, 1993
- Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cellsCell, 1992
- Purification of DNA from formaldehyde fixed and paraffin embedded human tissueBiochemical and Biophysical Research Communications, 1985