Abstract
BackgroundTelomeres, repetitive DNA capping ends of eukaryotic chromosomes, are important in the maintenance of genomic integrity. Perturbed telomeres are common features of many human malignancies, including colorectal cancer.MethodsTelomere length (TL), measured by a Monochrome Multiplex Real-Time qPCR, was investigated in tumour tissues, adjacent mucosa, and blood from patients with colorectal cancer with different clinicopathological features and its impact on patient survival. TL was also measured in a limited number of liver metastases, non-cancerous liver tissues or corresponding tissues from the same patients.ResultsTL in tumour tissues was shorter than in the adjacent mucosa (P < 0.0001). Shorter TL was observed in tumours with lower stage than in those with advanced stages (P = 0.001). TL was shorter in tumours at the proximal than at the distal sites of the colon (P < 0.0001). Shorter TL was also associated with microsatellite instability (P = 0.001) and mucinous tumour histology (P < 0.0001). Patients with a smaller TL ratio between tumour tissues and the adjacent mucosa were associated with increased overall survival (P = 0.022). Metastasised tumours had shorter telomeres than the adjacent non-cancerous liver tissues (P = 0.0005).ConclusionsOverall, the results demonstrate differences in TL between tumours and the adjacent mucosa, between tumours located at different sites and association with patient survival.
Highlights
Telomeres, repetitive DNA capping ends of eukaryotic chromosomes, are important in the maintenance of genomic integrity
Shorter Telomere length (TL) in tumour tissue (i.e. TL ratio < 1) was observed in tumours from 74% patients, while for the remaining 26% of colorectal cancer (CRC) patients, tumours had a longer TL than the adjacent mucosa
We did not find any difference between TL in peripheral blood lymphocytes (PBL) (n = 164, 0.76 [0.56–1.04]) and the corresponding tumour tissues (0.78 [0.58–1.04], P = 0.2)
Summary
Repetitive DNA capping ends of eukaryotic chromosomes, are important in the maintenance of genomic integrity. METHODS: Telomere length (TL), measured by a Monochrome Multiplex Real-Time qPCR, was investigated in tumour tissues, adjacent mucosa, and blood from patients with colorectal cancer with different clinicopathological features and its impact on patient survival. RESULTS: TL in tumour tissues was shorter than in the adjacent mucosa (P < 0.0001). Patients with a smaller TL ratio between tumour tissues and the adjacent mucosa were associated with increased overall survival (P = 0.022). Metastasised tumours had shorter telomeres than the adjacent non-cancerous liver tissues (P = 0.0005). Telomere length (TL) is affected by the genotoxic effect of environmental and intracellular DNA-damaging agents, including anticancer drugs.[1,2,3] Telomere shortening correlates with age.[4] Tumour cells due to increased proliferation undergo faster telomeric attrition than non-cancerous somatic cells. The rejuvenated telomerase preferentially stabilises the shortest telomeres and critically short telomeres can lead to the formation of anaphase bridges through breakage–fusion–bridge cycles that contributes to chromosome instability (CIN).[5]
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