Chromatin accessibility reveals regulatory pathways in oesophageal adenocarcinoma

Abstract

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer, which is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood although genomic sequencing studies have identified several genes encoding chromatin remodelling enzymes that are frequently mutated in OAC. This finding is consistent with the knowledge that one important change that occurs in cancer cells is a reprogramming of the chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells. Furthermore we have developed the technique of ATAC-seq to allow human tissue biopsies to be processed to identify chromatin changes that occur in real life cancer samples, identifying HNF4a GATA4, GATA6 and FOXA2 as putative regulatory transcription factors in a subset of OAC.

Date of Award	28 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Andrew Sharrocks (Main Supervisor) & Yeng Ang (Co Supervisor)