REAL-TIME PCR QUANTIFICATION OF HUMAN DKC1 EXPRESSION IN COLORECTAL CANCER

Mutations in the highly conserved human DKC1 gene cause the rare genetic disease X-linked recessive dyskeratosis congenita (X-DC). X-DC patients and DKC1 hypomorphic mutant mice show an increased susceptibility to cancer, so that it has been suggested that DKC1 can act as potent tumor suppressor. The nucleolar protein encoded by DKC1, named dyskerin, is one of the core components of the nucleolar ribonucleoprotein particles which include the small nucleolar RNAs belonging to the H/ACA family. Within H/ACA snoRNPs, dyskerin is known to play a crucial role in rRNA processing and pseudouridylation, being able to act as pseudouridine synthase. In addition, dyskerin has been recently identified as an essential component of the catalytically active human telomerase complex, together with the human telomerase reverse trascriptase (TERT) and the RNA component of telomerase. Since TERT has been indicated as a potential biomarker for colorectal cancer, we wished to evaluate whether dyskerin and TERT mRNA levels were similarly variable in colorectal cancer. In this study, matched samples of tumors and adjacent non-tumorous mucosa from 8 colorectal carcinomas were collected, and Real-time polymerase chain reaction was used to quantitate DKC1 and TERT expression levels. We found that in the colorectal adenocarcinomas DKC1 mRNA level was significantly higher than in the corresponding non-tumor mucosa (p=0.0004, one-sided t test). Instead, TERT exhibited a variable mRNA level, although in most cases it was up-regulated respect to the matched controls (p=0.066, one-sided t test). These data support the view that DKC1 expression may be considered a less variable and more sensible marker than TERT for proliferative colon disorders. Although analysis of a more exhaustive series of tumors is needed, we suggest that the evaluation of DKC1 expression can provide a useful clue in the diagnosis and prognosis of colorectal cancer.