Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genomic instability in pre-neoplastic colonic lesions


Genomic instability is a characteristic of most cancers and it is argued that genomic instability is a driving force for tumorigenesis. Data herein demonstrate that genomic instability, as evidenced by microsatellite instability (MSI) and promoter methylation of DNA mismatch repair genes, is common in individual glands of pre-malignant colorectal lesions and raises interesting questions about the role of MSI in the development of colorectal carcinoma.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout


  1. Beggs AD, Domingo E, Abulafi M, Hodgson SV, Tomlinson IPM . A study of genomic instability in early preneoplastic colonic lesions. Oncogene (e-pub ahead of print 17 December 2012; doi:10.1038/onc.2012.584.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993; 104: 1535–1549.

    Article  CAS  PubMed  Google Scholar 

  3. Lynch HT, de la Chapelle A . Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 1999; 36: 801–818.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Salovaara R, Loukola A, Kristo P, Kaariainen H, Ahtola H, Eskelinen M et al. Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J Clin Oncol 2000; 18: 2193–2200.

    Article  CAS  PubMed  Google Scholar 

  5. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H et al. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 1997; 57: 808–811.

    CAS  PubMed  Google Scholar 

  6. Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 1998; 95: 6870–6875.

    Article  CAS  PubMed  Google Scholar 

  7. Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ et al. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res 1998; 58: 3455–3460.

    CAS  PubMed  Google Scholar 

  8. Lothe RA, Peltomäki P, Meling GI, Aaltonen LA, Nystrom-Lahti M, Pylkkanen L et al. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 1993; 53: 5849–5852.

    CAS  PubMed  Google Scholar 

  9. Kim H, Jen J, Vogelstein B, Hamilton SR . Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 1994; 145: 148–156.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Blount PL et al. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res 2004; 64: 7629–7633.

    Article  CAS  PubMed  Google Scholar 

  11. Bodmer W, Bielas JH, Beckman RA . Genetic instability is not a requirement for tumor development. Cancer Res 2008; 68: 3558–3560 discussion 3560–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kuismanen SA, Holmberg MT, Salovaara R, Schweizer P, Aaltonen LA, de la Chapelle A et al. Epigenetic phenotypes distinguish microsatellite-stable and -unstable colorectal cancers. Proc Natl Acad Sci USA 1999; 96: 12661–12666.

    Article  CAS  PubMed  Google Scholar 

  13. Nakagawa H, Nuovo GJ, Zervos EE, Martin EW, Salovaara R, Aaltonen LA et al. Age-related hypermethylation of the 5′ region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res 2001; 61: 6991–6995.

    CAS  PubMed  Google Scholar 

  14. Datta RS, Gutteridge A, Swanton C, Maley CC, Graham TA . Modelling the evolution of genetic instability during tumour progression. Evol Appl 2013; 6: 20–33.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to J Stebbing.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shaw, J., Graham, T. & Stebbing, J. Genomic instability in pre-neoplastic colonic lesions. Oncogene 32, 5331–5332 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links