Telomeres, telomerase and colorectal cancer

Figure 1 Model of telomere/telomerase interplay in the carcinogenesis of colorectal cancer. Telomere shortening is mainly caused by cell proliferation in preneoplastic lesions. Erosion of telomeres may be accelerated by mutations in specific genes, such as the adenomatous polyposis coli (APC) gene or DNA mismatch repair (MMR) system genes. The activation of telomerase reverse transcriptase (TERT), the catalytic unit of the telomerase, occurs during the adenoma-carcinoma sequence; TERT and telomerase activity levels increase with tumour progression. Inserts: Immunohistochemical analysis of TERT expression in stage I (left) and stage IV (right) tumours. Mayer's haematoxylin counterstaining; original magnification × 20.

Figure 2 Representative panels of telomere length and telomerase reverse transcriptase levels. A: Relative telomere length in tumours (K) and adjacent mucosa (N) according to tumour stages I (30 samples), II (45 samples), III (29 samples), and IV (29 samples). The cases included those reported in Rampazzo et al[41]. Telomere length was significant shorter in tumours than in adjacent mucosa (^bP < 0.0001) at all tumour stages, but telomere lengths did not significantly differ with tumour stage. Relative telomere length was estimated using real-time polymerase chain reaction (real-time PCR)[41]; B: Telomerase reverse transcriptase (TERT) levels in tumours (K) and adjacent mucosa (N) according to tumour stages I (K: 25 samples, N: 17 samples), II (K: 35 samples; N: 10 samples), III (K: 15 samples; N: 5 samples), and IV (K: 30 samples; N: 22 samples). The cases included those reported in Terrin et al[55]. TERT levels were significantly higher in tumours than in adjacent mucosa and significantly increased (^bP < 0.01) with tumour stage. TERT levels were estimated using real-time PCR[41,55]; C: Plasma TERT levels before and after the chemoradiotherapy prior to surgery in responders (35 samples) and non-responders (42 samples) with rectal cancer. The cases included those reported in Pucciarelli et al[84]. TERT levels in plasma were estimated using real-time PCR[84]. Boxes and whiskers: 25^th-75^th and 10^th-90^th percentiles, respectively; the median is the central line in each box.