Epigenetic and Phenotypic Profiling of Urothelial Carcinoma

Sammanfattning: Precise spatial and temporal regulation of gene expression programs is a prerequisite for multicellular life. Since the discovery of DNA as the carrier of genetic information, a key question in biology has been how these hard coded instructions are read and regulated to maintain cellular and organismal homeostasis. Understanding the mechanisms and processes governing gene and genome regulation are key to solving many of the outstanding problems in medicine as all forms of disease represent a breakdown of homeostasis. The concept of epigenetics, how the genotype gives rise to different phenotypes in organismal development, entered the scientific vernacular in the first half of the 20th century. Increasing knowledge of the processes underlying genome regulation has shifted the core emphasis of epigenetic research from the phenotypic level and towards the molecular basis of genome regulation. This thesis provides a brief history and description of the concept of epigenetics while summarizing basic aspects of genome regulation in order to serve as a general backdrop for the larger biological context of the included works. The overall aim of the papers included in this thesis has been to study the epigenetic and phenotypic landscape of urothelial carcinoma with the goal of gaining a fuller understanding of the molecular alterations underlying the full spectrum of the disease.