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Research Paper | February 1, 2014

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Aberrant methylation in promoter region induced silencing of P16/NK4a in colorectal cancer in Iranian patients

Jamshid Mehrzad, Mohammad Hashemi, Mahmodreza Jamshidi, Alireza motavalizadekakhki, Jafar Saeidi, Mahdieh Mohammaditabr, Arezoo Sadat Khafi, Behzad Taheri Moghaddam

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J. Bio. Env. Sci.4(2), 94-103, February 2014

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Abstract

Aberrant methylation in promoter regions of genes might lead to change gene functions and result in cancer. Hence, biomarker identification for aberrant methylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of colorectal cancer (CRC). The aim of the present study was to detection correlation between methylation status in promoter region of P16/NK4a with P16/NK4a expression level, CRC occurence and with demographic and clinocopathological characteristics of CRC. Methylation status in promoter region of P16/NK4a was assayed by methylation-specific polymerase chain reaction (MS-PCR) and P16/NK4a gene expression was performed by real time quantitative PCR (qPCR). RNA from embedded paraffin sections of colorectal tissue (in 70 sporadic colorectal tumors as well as adjoining and normal tissue specimens) was reverse transcribed, quantified and analyzed by Q-PCR. Aberrant promoter methylation of p16 gene was detected in 27 (38.6%) tumor samples and in 8 (11.4%) adjacent normal tissues. Thus, aberrant promoter methylation of p16 is significantly correlated with CRC occurance. Aberrant promoter methylation was found significantly associated with tumor stage II (P=0.000), but not with other clinocopathological and demographic characteristics. P16/INK4a expression level in tumor tissues was 8.6-fold more than normal adjacent tissues. In conclusion, this study has identified aberrant promoter methylation of P16/INK4a was significantly correlated with CRC, because aberrant promoter methylation effects on P16/INK4a expression. Our approaches revealed P16/INK4a can be as a potential biomarker for CRC as diagnostic, prognostic and therapeutic targets in the future.

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Aberrant methylation in promoter region induced silencing of P16/NK4a in colorectal cancer in Iranian patients

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