Germline mutations of TP53 gene can be a key factor in prostate cancer genesis

Background The TP53 gene is one of the most important agent of the DNA repair pathway. Alterations of this gene have been found in more than 50% of human primary tumors including prostate cancer. The germline TP53 mutation is responsible for Li-Fraumeni syndrome, which is associated with a predisposition to several cancers. Objective The aim of this study is to investigate whether germline alterations of exon 5 of TP53 gene could be detected in the blood of known men with prostate cancer and to assess the potential association between the genomic alteration affecting this gene and clinico-pathological characteristics of the patients. Material and methods Fourty eight blood samples from men diagnosed with prostate cancer were analyzed for TP53 germline mutations and confirmed by Sanger sequencing. The frequency and distribution of high-frequency mutations were analyzed according to the pathological criteria of the patients and computational study was performed to assess the affect of new mutations. Results The Sanger sequencing revealed that 79% of the population studied carry mutations, and a total of 137 mutations were identified including 115 new mutations. Frameshift mutations were the most frequent ; the mutation c.392delA was recorded in fifteen cases (31%) ; the mutations c.383delC and c.432delG observed at a frequency of 12.5% and 10% respectively. The most frequent missense mutation was the variant c.502C > A (p.His168Asn) identified in eleven patients (23%). One nonsense mutation was identified in one patient and result to a stop codon in position 126 (tyrosine). All codons affected by these alterations are part of the DNA binding domain of the protein. Conclusion The germline mutation frequency observed in prostate cancer patient, and the new mutations recorded in TP53 gene, could be in favor of a potential association of genomic alterations in this gene and prostate cancer genesis, there by constituting a tool, similar to other genes in the DNA repair pathway such as BRCA1 and BRCA2. This could contribute to the advancement of diagnosis and therapeutic strategies for prostate cancer.