Michal Kroupa1,2, Sivarama Krishna Rachakonda3, Vaclav Liska4, Nalini Srinivas3, Marketa Urbanova5,6, Katerina Jiraskova5,6, Michaela Schneiderova7, Ondrej Vycital4, Veronika Vymetalkova5,4,6, Ludmila Vodickova5,4,6, Rajiv Kumar3, Pavel Vodicka8,9,10. 1. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic. michal.kroupa@iem.cas.cz. 2. Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. michal.kroupa@iem.cas.cz. 3. Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. 4. Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. 5. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic. 6. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. 7. Department of Surgery, General University Hospital in Prague, Prague, Czech Republic. 8. Department of Molecular Biology of Cancer, Institute of Experimental Medicine, The Czech Academy of Sciences, Prague, Czech Republic. pavel.vodicka@iem.cas.cz. 9. Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. pavel.vodicka@iem.cas.cz. 10. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. pavel.vodicka@iem.cas.cz.
Abstract
BACKGROUND: Telomeres, 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. 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. TL was also measured in a limited number of liver metastases, non-cancerous liver tissues or corresponding tissues from the same patients. RESULTS: TL 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). CONCLUSIONS: Overall, the results demonstrate differences in TL between tumours and the adjacent mucosa, between tumours located at different sites and association with patient survival.
BACKGROUND: Telomeres, repetitive DNA capping ends of eukaryotic chromosomes, are important in the maintenance of genomic integrity. Perturbed telomeres are common features of many humanmalignancies, including colorectal cancer. 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. TL was also measured in a limited number of liver metastases, non-cancerous liver tissues or corresponding tissues from the same patients. RESULTS: TL 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). CONCLUSIONS: Overall, the results demonstrate differences in TL between tumours and the adjacent mucosa, between tumours located at different sites and association with patient survival.
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