Germline mutations of the putative tumor suppressor gene PTEN/MMAC1 as molecular biomarker in prostate cancer

The phosphatase and tensin homolog gene (PTEN) is a key tumor suppressor gene, which signals down the phosphoinositol-3-kinase/Akt pathway and affects cell cycle arrest and apoptosis. Alteration and mutation of the PTEN gene have been found in several types of tumors, including prostate cancer. Germline mutations of this gene are associated with the PTEN Hereditary Tumor Syndromes (PHTS), a hereditary overgrowth and cancer predisposition disorder. The present study aimed to determine whether germline alterations in exon 5 of the PTEN gene could be detected in the blood of men known to have prostate cancer, in order to uncover any aberrations that affect this key gene, which is likely involved in the cancer process.

Forty-eight blood samples from men diagnosed with prostate cancer were analyzed for germline mutations in the PTEN and confirmed by Sanger sequencing. The Sanger sequencing results revealed that 69% of the population carries mutations, including several new mutations and known mutations. The Frameshift mutations: c.459delT variant was detected with a frequency of 12.5%, and four frameshift variants were observed with frequencies of 8% each: c.304delA, c.338delG, c.439_440insG, c.457delG. For the missense mutations, the most frequent variant was c.473 T > C (p.Val158Ala), recorded in four patients (8%), while the variants c.361G > C (p.Ala121Pro) was detected in 6% of the population. There was no significant difference between mutation carriers and non-carriers regarding clinicopathological features. Our results provide insight into novel mutations identified in the PTEN gene in prostate cancer. This presents a new opportunity to focus on and highlight key genes for clinical exploration as potential biomarkers in the diagnosis and management of prostate cancer.