MUTATIONAL ANALYSIS OF PTEN GENE IN PAKISTANI BREAST CANCER PATIENTS

Abstract

Breast cancer is defined as the uncontrolled cell division in breast tissue. Breast cancer can originate in any part of the breast and is categorized into different types. Breast cancer is the most prevalent type of cancer among females globally and every eighth female is at risk of breast cancer. Breast cancer is a multifactorial disorder with genetic factors being major risk factor for disease development. Different genes including tumour suppressor genes are involved in breast cancer development. Phosphatase and Tensin homolog (PTEN) acts as a phosphatase, which dephosphorylate phosphor-peptides and phospholipids. As phosphatase, it regulates cell cycle which prevents rapid growth and division of cells. The aim of the study was detection of single nucleotide polymorphisms (SNPs) in PTEN gene among breast cancer Pakistani population. For this purpose, DNA was extracted from blood samples and was electrophoresed on 1% gel, later amplified by polymerase chain reaction. Variations in Exon 4, Exon 5 of the PTEN gene were observed by performing single stranded conformational polymorphism(SSCP) followed by Sanger sequencing. BIOEDIT and Mutation Taster were used to analyse the sequencing results by aligning the sequences with reference sequence NG_007466.2 from NCBI. Two novel disease causing mutation were detected in Exon 4 of PTEN at chromosome position chr10:89690839_89690839delT and chr10:89690825A>TN/A. Both mutations were non-synonymous, hence might have alteration in PTEN. Such SNPs in tumour suppressor protein due to PTEN gene might affect the cell cycle. Based on risk factors, the age groups above 40 years; 58-72 years (OR: 2.8615 [1.5668 to 5.2259] p value = 0.0006) and 73-87 years (OR: 3.4561 [0.9367 to 12.7519] p value = 0.0626) and a positive family history of the breast cancer (OR: 5.7486 [1.9361 to 17.0689] p value = 0.0016) were significantly associated with the risk of breast cancer development. Beside known BRAC1 and BRAC2 pathogenic genes, novel SNPs identified in local breast cancer patients indicates that other genes like PTEN should be investigated for its role in oncogenesis. Such novel variants are addition to the knowledge of breast cancer as predictive marker to assess the risk of breast cancer development.