Abstract : The endoribonuclease L (RNASEL) is the effector of the 2–5A system, a major enzymatic pathway regulated by interferons, encodes a ribonuclease that plays a significant role in the apoptotic pathway. RNASEL gene has been traditionally associated with Hereditary Prostate Cancer 1 and disease severity. Hereditary genetic alterations in RNASEL affect apoptotic responses, such mutations could possibly contribute to malignancy. In order to investigate the genetic alterations of the RNASEL gene in prostate cancer patients and correlation with clinical and pathological parameters, DNA samples from 100 blood samples from prostate cancer patients were genotyped and confirmed by Sanger sequencing. The frequency and distribution of high frequent mutations were determined and correlated with the patient’s tumor characteristics. Among 100 patients 74 % were carriers to one or more mutations in RNASEL gene. Our results revealed the detection of the RNASEL germline mutations, Arg462Gln variant, a common missense variant causing threefold reduction in enzymatic activity, with a high frequency (58%) in the Moroccan men with prostate cancer. In addition, One of the 100 patients have a nonsense substitution with 1% frequency and for synonymous mutations two substitutions have been detected, c.1263T>C and c.1416T>C with 3% and with 2% frequency rate respectively and frameshift mutations frequency were c.1250_1251insT in 7 patients, c.1256delC in 4% of patients while c.1257delA, c.1351delG and c.1395delG 3 have the same frequency 3%. Five of the most eight frequent missenses detected in our study were predicted to alter the RNASEL protein in all three powerful servers (SIFT, PolyPhen2 and PredictSNP), Those missense variants probably reduce the function of RNASEL as kinase enzyme leading to a defect in protein pathway as tumor suppressor genes. Interestingly, those missense variants were located in the RNASEL protein kinase-like domain. No significant differences between carriers and non-carriers of common mutations detected regarding Pathological Gleason score, PSA concentration, Tumor stage and age at diagnosis, [p > 0.05]. family history data and Clinical significance of mutations detected on prostate tumors progression can be investigated in future analysis. Our findings revealed novel RNASEL alterations in prostate cancer patients and it could be associated with cancer development..
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