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Telomerase activation in colorectal carcinogenesis
P Yan1, E P Saraga, H Bouzourene
1Institute of Pathology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
The Journal of Pathology
|November 5, 1999
Summary
Telomerase activation is detected in most colorectal cancers and high-grade adenomas, but not normal tissues. This suggests telomerase activation is a key step in colorectal cancer development, occurring during dysplasia progression.
Area of Science:
- Molecular Biology
- Oncology
- Gastroenterology
Background:
- Telomerase activity is typically absent in somatic cells but present in germ cells and reactivated in most cancers.
- The colorectal adenoma-carcinoma sequence provides a model to study multistep tumorigenesis and telomerase activation timing.
Purpose of the Study:
- To determine the stage at which telomerase is activated during colorectal tumorigenesis.
- To investigate the relationship between telomerase activity and dysplasia grade in colorectal adenomas.
Main Methods:
- Telomeric Repeat Amplification Protocol (TRAP) assay was used to measure telomerase activity.
- 96 colorectal tissue samples (50 carcinomas, 31 adenomas, 15 normal) were analyzed.
- rRNA integrity was verified to ensure assay reliability.
Main Results:
- No telomerase activity was detected in normal colorectal tissues.
- Telomerase was active in all analyzed carcinomas (25/25) and 47% of adenomas (14/30).
- Telomerase activation in adenomas strongly correlated with high-grade dysplasia (p<0.0001).
Conclusions:
- Telomerase activation appears to be an obligatory step in colorectal carcinogenesis, occurring during the transition from low-grade to high-grade dysplasia.
- Telomerase activation seems to precede K-ras mutation but follow p53 mutation in the adenoma-carcinoma sequence.