| Theme |
Molecular pathology of colorectal cancer for clinicians |
| Title |
Telomeres, telomerase in colon cancer |
| Author |
Norimasa Matsutani |
First Dept. of Pathology, Hiroshima Univ. School of Medicine |
| Author |
Hiroki Kuniyasu |
First Dept. of Pathology, Hiroshima Univ. School of Medicine |
| Author |
Wataru Yasui |
First Dept. of Pathology, Hiroshima Univ. School of Medicine |
| [ Summary ] |
Telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex required for the protection and replication of chromosome ends. Telomere maintenance requires a homeostatic balance between addition of telomeric sequences by telomerase, repression of telomerase, and persistent capping activity by telomeric proteins and structures. Telomeric repeat binding factor 1 (TRF 1) and 2 (TRF 2) may play key roles in the maintenance of telomere function. TRF1 negatively regulates telomere elongation, while TRF2 protects the chromosome ends by inhibiting end-to-end fusions. Other telomere components, tankyrase, TIN2 and the double-strand DNA breaks repair enzymes, Mrell, Rad5O, NBS1 are also necessary for telomere maintenance. A high telomerase activity rate is detected in most colorectal cancers, regardless of tumor staging or histological differentiation. Human telomerase reverse transcriptase (hTERT) expression is also correlated with telomerase activity. Twenty-seven percent and twenty-three percent of colorectal cancers express TRF1 and TRF2 at higher levels than non-neoplastic mucosa, respectively. Twenty percent of colorectal adenomas with strong telomerase activity show marked nuclear atypia, although structural atypia is mild. This suggests that morphological change is associated with malignant potential. |