Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Nov;85(10):1492–1498. doi: 10.1054/bjoc.2001.2095

Colorectal cancer genomics: evidence for multiple genotypes which influence survival

P H Rooney 1, A Boonsong 1, J A McKay 1, S Marsh 1, D A J Stevenson 2, G I Murray 3, S Curran 3, N E Haites 1,2, J Cassidy 1, H L McLeod 1
PMCID: PMC2363933  PMID: 11720434

Abstract

Colorectal cancer (CRC) is a leading cause of cancer death and the mechanism for variable outcome in this disease is not yet fully understood. It is hypothesized that differences in the genetic make-up of tumours may be partially responsible for the differences observed in survival among same staged individuals for this disease. In this study the tumour genomes of 29 consecutive patients undergoing surgery for Dukes' C CRC were assessed by comparative genomic hybridization (CGH). In addition, the CGH profiles from the tumours were compared with those from eight colorectal cell lines. Great variation in genetic grade (all detectable aberrations i.e., loss + gain) was observed in 29 Dukes' C colorectal tumours by CGH (median four aberrations per tumour, range 0–20). Gain was found in 76% and loss in 41% of tumours. The most frequently observed regions of gain were 13q (27.6%), 20q (27.6%), 7p (24.1%), 8q (24.1%), and 1q (20.7%) and loss were 18q (31%), 4q (20.7%), 17p (20.7%), 18p (20.7%), and 15q (20.1%). None of these specific genomic aberrations were associated with patient survival. However, patients with more than two aberrations had a better survival than patients with fewer regions of loss and gain (P = 0.02). CRC cell lines had similar regions of loss or gain as the tumours. However, the frequency of genomic aberrations was much greater in the CRC cell lines. Although genomic change in CRC is relevant to the survival of patients with Dukes' C CRC, careful analysis is required to identify cell lines which are representative models of CRC genomics.© 2001 Cancer Research Campaign  http://www.bjcancer.com

Keywords: CGH, colo-rectal tumours, cell lines, survival, cancer genomics

Full Text

The Full Text of this article is available as a PDF (81.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Al-Mulla F., Keith W. N., Pickford I. R., Going J. J., Birnie G. D. Comparative genomic hybridization analysis of primary colorectal carcinomas and their synchronous metastases. Genes Chromosomes Cancer. 1999 Apr;24(4):306–314. doi: 10.1002/(sici)1098-2264(199904)24:4<306::aid-gcc3>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  2. Barth T. F., Benner A., Bentz M., Döhner H., Möller P., Lichter P. Risk of false positive results in comparative genomic hybridization. Genes Chromosomes Cancer. 2000 Jul;28(3):353–357. doi: 10.1002/1098-2264(200007)28:3<353::aid-gcc15>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  3. Boring C. C., Squires T. S., Tong T. Cancer statistics, 1993. CA Cancer J Clin. 1993 Jan-Feb;43(1):7–26. doi: 10.3322/canjclin.43.1.7. [DOI] [PubMed] [Google Scholar]
  4. Cahill D. P., Kinzler K. W., Vogelstein B., Lengauer C. Genetic instability and darwinian selection in tumours. Trends Cell Biol. 1999 Dec;9(12):M57–M60. [PubMed] [Google Scholar]
  5. Cahill D. P., Lengauer C., Yu J., Riggins G. J., Willson J. K., Markowitz S. D., Kinzler K. W., Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998 Mar 19;392(6673):300–303. doi: 10.1038/32688. [DOI] [PubMed] [Google Scholar]
  6. Collins C., Rommens J. M., Kowbel D., Godfrey T., Tanner M., Hwang S. I., Polikoff D., Nonet G., Cochran J., Myambo K. Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8703–8708. doi: 10.1073/pnas.95.15.8703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. De Angelis P. M., Clausen O. P., Schjølberg A., Stokke T. Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes. Br J Cancer. 1999 May;80(3-4):526–535. doi: 10.1038/sj.bjc.6690388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  9. Georgiades I. B., Curtis L. J., Morris R. M., Bird C. C., Wyllie A. H. Heterogeneity studies identify a subset of sporadic colorectal cancers without evidence for chromosomal or microsatellite instability. Oncogene. 1999 Dec 23;18(56):7933–7940. doi: 10.1038/sj.onc.1203368. [DOI] [PubMed] [Google Scholar]
  10. Gryfe R., Kim H., Hsieh E. T., Aronson M. D., Holowaty E. J., Bull S. B., Redston M., Gallinger S. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000 Jan 13;342(2):69–77. doi: 10.1056/NEJM200001133420201. [DOI] [PubMed] [Google Scholar]
  11. Hawkins N. J., Tomlinson I., Meagher A., Ward R. L. Microsatellite-stable diploid carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer. Br J Cancer. 2001 Jan;84(2):232–236. doi: 10.1054/bjoc.2000.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jones C., Payne J., Wells D., Delhanty J. D., Lakhani S. R., Kortenkamp A. Comparative genomic hybridization reveals extensive variation among different MCF-7 cell stocks. Cancer Genet Cytogenet. 2000 Mar;117(2):153–158. doi: 10.1016/s0165-4608(99)00158-2. [DOI] [PubMed] [Google Scholar]
  13. Kallioniemi A., Kallioniemi O. P., Piper J., Tanner M., Stokke T., Chen L., Smith H. S., Pinkel D., Gray J. W., Waldman F. M. Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2156–2160. doi: 10.1073/pnas.91.6.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kallioniemi A., Kallioniemi O. P., Sudar D., Rutovitz D., Gray J. W., Waldman F., Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 1992 Oct 30;258(5083):818–821. doi: 10.1126/science.1359641. [DOI] [PubMed] [Google Scholar]
  15. McLeod H. L., Murray G. I. Tumour markers of prognosis in colorectal cancer. Br J Cancer. 1999 Jan;79(2):191–203. doi: 10.1038/sj.bjc.6690033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moertel C. G., Fleming T. R., Macdonald J. S., Haller D. G., Laurie J. A., Tangen C. M., Ungerleider J. S., Emerson W. A., Tormey D. C., Glick J. H. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321–326. doi: 10.7326/0003-4819-122-5-199503010-00001. [DOI] [PubMed] [Google Scholar]
  17. Pisani P., Parkin D. M., Bray F., Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 1999 Sep 24;83(1):18–29. doi: 10.1002/(sici)1097-0215(19990924)83:1<18::aid-ijc5>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  18. Reiss M., Gamba-Vitalo C., Sartorelli A. C. Induction of tumor cell differentiation as a therapeutic approach: preclinical models for hematopoietic and solid neoplasms. Cancer Treat Rep. 1986 Jan;70(1):201–218. [PubMed] [Google Scholar]
  19. Ried T., Knutzen R., Steinbeck R., Blegen H., Schröck E., Heselmeyer K., du Manoir S., Auer G. Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors. Genes Chromosomes Cancer. 1996 Apr;15(4):234–245. doi: 10.1002/(SICI)1098-2264(199604)15:4<234::AID-GCC5>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  20. Rooney P. H., Murray G. I., Stevenson D. A., Haites N. E., Cassidy J., McLeod H. L. Comparative genomic hybridization and chromosomal instability in solid tumours. Br J Cancer. 1999 May;80(5-6):862–873. doi: 10.1038/sj.bjc.6690433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rooney P. H., Stevenson D. A., Marsh S., Johnston P. G., Haites N. E., Cassidy J., McLeod H. L. Comparative genomic hybridization analysis of chromosomal alterations induced by the development of resistance to thymidylate synthase inhibitors. Cancer Res. 1998 Nov 15;58(22):5042–5045. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES