ABSTRACT
B-Raf proto-oncogene has been found in a variety of neoplasms. BRAF stimulation can promote tumour proliferation through the activation of the MAP/ERK kinase pathway. This study aimed to determine the germline spectra of BRAF and the association with pathological criteria of prostate tumours. Methods: Fifty blood samples from men treated with prostate cancer were analyzed for BRAF germline mutations and confirmed by Sanger sequencing, in addition, to establishing the frequencies and clinical correlations of frequent mutations in the BRAF gene for both exon 11 and exon 15. The frequency and distribution of high-frequency mutations were analyzed according to the pathological criteria of the patients. Results: Frameshift mutations: c.1628_1629insA and c.1624_1625insT with a frequency of (46%) and (18%), respectively, Nonsense mutations: c.1181C>A (p.Ser394Ter) was detected in one patient, missense mutations: c.1226A>G (p.Gln409Arg), c.1270T>C (p.Trp424Arg), c.1270_1271delins2 (p.Trp424Leu), with a frequency of (4%) were detected. There was no significant difference between mutation carriers and non-carriers regarding medical and surgical history, but prostate-specific antigen concentration was significantly different between the two groups. Conclusion: The results of this study elucidate the presence and involvement of germline mutations in prostate cancer, which could serve as a potential indicator for the diagnosis and therapeutic management of prostate cancer in the population studied.
ABSTRACT
The suspected roles of human Papillomavirus (HPV) and mouse mammary tumor virus (MMTV) infections in prostate tumor development were recently reported. To detect the frequency of HPV and MMTV-like infections and clinical correlates of tumor characteristics, DNA samples from 50 men treated at Teaching Hospital of Rabat City (Morocco) between June 2017 and February 2019, were genotyped and confirmed by Sanger sequencing. Eight infections of HPV18 and two infections of MMTV-like were detected, and 50% of patients were at a Gleason score of 6. A significant association between Gleason score and HPV or MMTV-like infection was noted (P=0.0008); 90% of patients with viral infections presented with T1 and T2 pathological stage tumors. Yet, no significant differences were found between infected and noninfected men regarding other pathological parameters including prostate-specific antigen (PSA), tumor histological stage, age at diagnosis and radical prostatectomy treatment (P=0.2179, 0.4702, 0.8101, and 0.9644, respectively). The molecular evolution of HPV and MMTV in comparison with previously aligned sequences was discussed. Our findings provide a highlight on the correlations between the clinical-pathological parameters of prostate tumors and HPV and MMTV infections. Prospective studies with a wide sample size are needed for more statistical clarification of the association between viral infections with prostate tumor criteria.