First Screening For Germline Variations In Exon 5 PTEN Gene and Their Contribution to Triple Negative Breast Cancer...

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype  associated with younger age, bigger tumor size, high grade tumor, high risk of tumor recurrence and death. PTEN is one of the tumor suppressor genes that have been analyzed to provide  its role in predisposition to  TNBC. The aim of this study was to screen germline variants in exon 5 of the PTEN gene in Algerian TNBC patients and to assess their association with the clinical characteristics of TNBC.

69 TNBC patients coming from different regions of eastern Algeria were analyzed for germline variants in exon 5 of the PTEN gene, among them 6 patients (8.69%) had a family history of breast cancer. Peripheral blood samples were obtained and genomic DNA was extracted from leukocytes using the salt-saturation method. Exon 5 was amplified by PCR and then sequenced. The resulted sequences were aligned against the reference sequence  available in GenBank. All detected variants were annotated using the Ensembl database and their pathogenicity was predicted according to their REVEL scores.

30 different variants in 27 (39.13%) of the 69 patients were identified. 6 missense variants were predicted to be likely benign and 24 variants were predicted to be pathogenic. Among them, 19 were missense variants, 2 were nonsense variants and 3 were frameshift variants, including 1 deletion and 2 novel insertions. The pathogenic variants occurred in 17 patients, who harbored between 1 and 4 pathogenic variants. No pathogenic variants were found in patients with a family history of breast cancer. The correlation between pathogenic variants and the clinical characteristics of TNBC patients was statistically insignificant.  Conclusion: The frequency of  pathogenic variants identified in the Algerian population is higher than that in other populations; however, they are not associated with susceptibility to TNBC.