Copy number variations as potential biomarkers for disease development in Breast Cancer

Abstract: Breast cancer is second foremost cause of deaths in women caused by malignant tumor.Comparing genetic profiles of cells surrounding the tumor and blood from same patient may reveal de‐novo somatic aberrations that may predispose normal cells to cancer cells. Two major types of genetic variations were discovered in human genome: single nucleotidepolymorphisms (SNPs) and more recently discovered copy number variations which are chromosomal segments ranging from kilobases to megabases. It is assumed that somaticcells are genetically identical. But it is unknown if CNVs arise in somatic cells. Somatic mosaicism is defined as genetic differences in the cells of a single individual which were developed from one fertilized egg. The purpose of this study was to identify and compare copy number variants in IFNAR1 loci of healthy uninvolved margin of breast tissue surrounding primary tumor and blood derived‐DNA of breast cancer patients by using Illumina SNPs array‐Human660W‐Quad.So far, long and very rigorous research on breast cancer explains only about 10% of all cases.This may signify unusual complexity of cancer and discovery of factors responsible for progression of cancer from healthy cells. Illumina SNPs genotyping of blood and cells surrounding tumor indicated the occurrence ofchanges in the region connected to IFNAR1 gene loci. Variations in IFNAR1 loci formed the base for detailed investigation of expected aberrations. The amplification of DNA fragments and deeper investigations were performed to identify and confirm the differences in genotype between blood and cells surrounding the tumor by cloning, restriction digestion and Sanger’s sequencing. The results noticeably confirmed the presence of somaticmosaicism. We have identified aberrations occurring as variable number of tandem repeats (VNTRs) with length of 32 nucleotides.Consequently, the significant progress in research on cause of cancer carries development of applied technologies (next generation sequencing) that allow examining more number ofsamples in fewer instances with better precision.