Gut 52:1304-1307 doi:10.1136/gut.52.9.1304
  • Cancer

Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer

  1. R R Plentz1,
  2. S U Wiemann1,
  3. P Flemming2,
  4. P N Meier1,
  5. S Kubicka1,
  6. H Kreipe2,
  7. M P Manns1,
  8. K L Rudolph1
  1. 1Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover, Germany
  2. 2Department of Pathology, Medical School of Hannover, Germany
  1. Correspondence to:
    Dr K L Rudolph, Department of Gastroenterology, Hepatology, and Endocrinology, Medical School of Hannover, Carl-Neuberg-Str 1, 30625 Hannover, Germany;
  • Accepted 3 April 2003


Background and aims: Chromosomal instability is one of the most consistent markers of sporadic colorectal cancer in humans. There is growing evidence that telomere shortening is one of the mechanisms leading to chromosomal instability and cancer initiation.

Methods: To test this hypothesis, the telomere length of colorectal epithelial cells and cells from connective tissue was determined at the adenoma-carcinoma transition at the cellular level by quantitative fluorescence in situ hybridisation.

Results: Our study showed that the telomere fluorescence intensity of epithelial cells was significantly weaker at the earliest morphologically definable stage of carcinoma—high grade dysplasia with minimal invasive growth—compared with the surrounding adenoma. In contrast, cells from connective tissue had a similar telomere signal intensity at the carcinoma stage compared with the adenoma, and in turn cells from connective tissue had overall significantly stronger telomere fluorescence signals compared with epithelial cells.

Conclusions: These results demonstrate that short telomeres of epithelial cells characterise the adenoma-carcinoma transition during human colorectal carcinogenesis, suggesting that carcinomas arise from cells with critical short telomeres within the adenoma. Since the adenoma-carcinoma transition in colorectal cancer is characterised by an increase in chromosomal instability and anaphase bridges, our data support the hypothesis that short telomeres initiate colorectal cancer by induction of chromosomal instability.