Array-CGH analysis of microsatellite-stable, near-diploid bowel cancers and comparison with other types of colorectal carcinoma

Jones, Angela M. and Davison, Eleanor J. and Halford, Sarah E. R. and Fiegler, Heike and Gorman, Patricia A. and Roylance, Rebecca R. and Carter, Nigel P. and Tomlinson, Ian P. M. (2005) Array-CGH analysis of microsatellite-stable, near-diploid bowel cancers and comparison with other types of colorectal carcinoma. Oncogene, 24 (1). pp. 118-129. ISSN 0950-9232

Full content URL: http://dx.doi.org/10.1038/sj.onc.1208194

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Abstract

Microsatellite-stable, near-diploid (MSI-CIN-) colorectal carcinomas have been reported, but it is not clear as to whether these tumours form a discrete group or represent one end of the distribution of MSI-CIN+ cancers. In order to address this question, we screened 23 MSI-CIN- colorectal cancers for gains and losses using array-based comparative genomic hybridization (aCGH) based on large-insert clones at about 1 Mb density. We compared our findings with those from a small set of MSI+CIN+ cancers, and with our reported data from MSI-CIN+ and MSI+CIN- cancers. We found no evidence of any form of genomic instability in MSI-CIN- cancers. At the level of the chromosome arm, the MSI-CIN- cancers had significantly fewer gains and losses than MSI-CIN+ tumours, but more than the MSI+CIN- and MSI+CIN+ lesions. The chromosomal-scale changes found in MSI-CIN- cancers generally involved the same sites as those in MSI-CIN+ tumours, and in both cancer groups, the best predictor of a specific change was the total number of such changes in that tumour. A few chromosomal-scale changes did, however, differ between the MSI-CIN- and MSI-CIN+ pathways. MSI-CIN- cancers showed: low frequencies of gain of 9p and 19p; infrequent loss of 5q and a high frequency of 20p gain. Overall, our data suggested that the MSI-CIN- group is heterogeneous, one type of MSI-CIN- cancer having few (< or =6) chromosomal-scale changes and the other with more (> or =10) changes resembling MSI-CIN+ cancers. At the level of individual clones, frequent and/or discrete gains or losses were generally located within regions of chromosomal-scale changes in both MSI-CIN- and MSI-CIN+ cancers, and fewer losses and gains were present in MSI-CIN- than MSI-CIN+ tumours. No changes by clone, which were specific to the MSI-CIN- cancers, were found. In addition to indicating differences among the cancer groups, our results also detected over 50 sites (amplifications, potential homozygous deletion and gains or losses which extended over only a few megabases) which might harbour uncharacterized oncogenes or tumour suppressor loci. In conclusion, our data support the suggestion that some MSI-CIN- carcinomas form a qualitatively different group from the other cancer types, and also suggest that the MSI-CIN- group is itself heterogeneous.

Keywords:Colorectal Cancer, Array CGH
Subjects:C Biological Sciences > C420 Human Genetics
C Biological Sciences > C440 Molecular Genetics
C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
ID Code:28815
Deposited On:04 Oct 2017 10:30

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