title: Augmented telomerase activity, reduced telomere length and the presence of alternative lengthening of telomere in renal cell carcinoma: plausible predictive and diagnostic markers.
abstract: In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach.
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India.
authors.forename: Deeksha
authors.initials: D
authors.lastname: Pal
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India.
authors.forename: Ujjawal
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India.
authors.forename: Ragini
authors.initials: R
authors.lastname: Khajuria
authors.affiliation: Department of Urology, PGIMER, Chandigarh, India.
authors.forename: Shrawan Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Histopathology, PGIMER, Chandigarh, India.
authors.forename: Nandita
authors.initials: N
authors.lastname: Kakkar
authors.affiliation: Department of Biochemistry, PGIMER, Chandigarh, India. Electronic address: fateh1977@yahoo.com.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Prasad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism*; D059505:Telomere Homeostasis
chemical_list: D014408:Biomarkers, Tumor; D019098:Telomerase
keywords: ALT; PML bodies; TRAP; Telomerase; Telomere length