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Comparative analysis of exon 11 mutations of brca1 gene in regard to circulating tumor dna (ctdna) & genomic dna in a cohort of breast cancer patients in Pakistan

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Author: 
Kalsoom Ahtzaz, Mehak Ali and Dr. Adnan Arshad
Abstract: 

The aim of our study was to identify BRCA1 mutations in Pakistani population and direct comparison between circulating tumor DNA and genomic DNA of breast cancer patients. The complete screening of genomic DNA and ctDNA of 22 Patients for Exon 11 of 3426bp was costly and time consuming. Thus our method of choice was High Resolution Melt Curve Analysis (HRM). We analyzed and detected founder mutation (185delAG) in Exon 2 of BRCA 1 gene in genomic DNA of 30 patients with 2 negative controls by HRM. We found that a founder mutation was present in 15 patients, thus bringing the total contribution of BRCA 1, Exon 2 founder mutation to 50% in our study population. Contrary to one common mutation of BRCA 1 Exon 2, many variants are identified in exon 11. But interestingly we found that same variants were present in ctDNA of patients in 20 cases. Our data also showed that in 12 samples, ctDNA displayed variation that was not present in genomic DNA , which enable us to assume that ctDNA is a significant biomarker that can not only display mutations of genomic DNA but also evolution of tumor.

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