Novel Methylation Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-Muscle Invasive Bladder Cancer
BAUS ePoster online library. Bryan R. Jun 24, 2019; 259509; P2-5 Disclosure(s): Nil
Rik Bryan
Rik Bryan
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Abstract
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INTRODUCTION

High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery.
DNA methylation is reported as predictive of tumour/patient outcomes in numerous solid organ and haematological malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC that predict tumour behaviour at initial diagnosis to help guide patient management.

Patients/methods
21 primary initial diagnosis HR-NMIBC tumours (from the Birmingham BCPP cohort) were analysed by Illumina HumanMethylation450 BeadChip arrays, and subsequently bisulphite Pyrosequencing™. Seven had not recurred at one year after resection and 14 had recurred and/or progressed, despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing™.

RESULTS

Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Pyrosequencing™ validation across the 53 tumours showed hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within one year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values.

Conclusions
This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known one-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.
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