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  • Original Paper
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Heterogeneity studies identify a subset of sporadic colorectal cancers without evidence for chromosomal or microsatellite instability

Oncogene volume 18, pages 7933–7940 (1999)Cite this article

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.

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Acknowledgements

We are grateful to Harris Morrison of the Human Genetics Unit, MRC, Edinburgh for help and advice with CGH and to Joan Flanigan and Jennifer Doig for expert technical assistance. This study was funded by a Programme Grant from the Cancer Research Campaign [CRC] (Ref. no. 18201), the Medical Research Council and the Dr James and Bozena Bain fund.

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Authors and Affiliations

  1. Sir Alastair Currie CRC Laboratories, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    I B Georgiades, L J Curtis, R M Morris, C C Bird & A H Wyllie

  2. Department of Pathology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, UK

    C C Bird

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  1. I B Georgiades
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  2. L J Curtis
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Georgiades, I., Curtis, L., Morris, R. et al. Heterogeneity studies identify a subset of sporadic colorectal cancers without evidence for chromosomal or microsatellite instability. Oncogene 18, 7933–7940 (1999). https://doi.org/10.1038/sj.onc.1203368

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