Profiling of DNA Methylation and Single Nucleotide Polymorphism for Diagnosis, Prognosis and Targeting DNA Methyltransferases for Therapeutic Intervention of Breast Cancer

Abstract

Breast cancer being multifaceted disease constitutes a wide spectrum of histological and molecular variability in tumors. Now, in the wake-up of the Human Genome Project (HGP) several evidences recommend a marked plasticity adopted by tumor cells in modulating the tissue invasion and progression during multiple stages of metastasis. However, the task for the identification of these casualties in a cancer genome is complicated by the interplay of inherited genetic and epigenetic aberrations. These aberrations are like two sides of the same coin. Therefore, in this thesis we provide an extrapolate outlook to the sinister partnership between genetic and epigenetic aberrations in relevance to breast cancer. DNA methylation is a prototypical epigenetic parameter that lay ground in understanding the gene regulation and their intricate interactions in the normal and diseased state. However, when it is comprehended by the extensive study of the genomicand transcriptomic parameter, it leads to better understanding of complex traitarchitecture of disease aetiology. The key to our analysis holds in identification of effective model that enables in predicting the phenotypic traits and outcomes, elucidating the presence of diagnostic and prognostic biomarkers and generate an insight into genetic underpinnings of heritable complex traits. In view of this, we explored the emerging approaches based upon data integration and meta-dimensional analysis to deepen our understanding to the relationship between the genomic variations and human phenotypes. This integrated study comprised of Illumina 450 DNA methylation, Affymetrix SNP array and RNAseq dataset retrieved from the Cancer genome atlas (TCGA) portal which elaborated the biological and complex outlay in the diagnosis, prognosis and therapeutic implications of breast cancer.