Novel Epigenetic Biomarkers for the Barrett’s – Adenocarcinoma Sequence in Oesophageal Cancer

Dilworth, Mark (2016). Novel Epigenetic Biomarkers for the Barrett’s – Adenocarcinoma Sequence in Oesophageal Cancer. University of Birmingham. M.D.

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Abstract

Introduction
Oesophageal adenocarcinoma presents an ever increasing challenge to the NHS, with rising incidence and poor overall survival. There are few robust biomarkers available for this disease – either for detection or stratification. Barrett’s Oesophagus, a precursor to adenocarcinoma, is common. In the non-dysplastic setting, few patients will progress to cancer. There are no current biomarkers to aid in this stratification process.
Aims
To assess the role of methylation biomarkers in the context of diagnosis of adenocarcinoma and their role in tumour biology. To provide a methylation stratification tool in the identification of high risk non-dysplastic Barrett’s Oesophagus.
Methods
Genome wide methylation assessment was performed with validation using bisulphite pyrosequencing on carefully selected tissues to reveal novel methylation biomarkers
Results
Methylation of TRIM15, has been shown to be a robust biomarker in disease identification and has a role in tumour biology.
OR3A4, a long none coding RNA, has been identified as a way to reliably risk stratify the non-dysplastic Barrett’s patient and forms the first biomarker of this kind.
Conclusions
Methylation biomarkers play a key role in disease identification and risk of cancer development. They also appear to play a role in tumour biology.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):