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01-11-2016 | Brief Report

Analysis of the breast cancer methylome using formalin-fixed paraffin-embedded tumour

Authors: Ee Ming Wong, JiHoon E. Joo, Catriona A. McLean, Laura Baglietto, Dallas R. English, Gianluca Severi, Hui-Chen Wu, Mary Beth Terry, John L. Hopper, Roger L. Milne, Graham G. Giles, Melissa C. Southey

Published in: Breast Cancer Research and Treatment | Issue 1/2016

Abstract

Purpose

Aberrant DNA methylation occurs frequently in breast carcinogenesis. Tools for translational epigenetic studies of breast cancer involving formalin-fixed paraffin-embedded (FFPE) human tissues have now been developed. Few studies have measured genome-wide methylation in DNA derived from paraffin-embedded tumour tissues and compared the DNA methylation in corresponding adjacent non-tumour ductal epithelium (ADJ_NT). These studies are technically challenging due to the spectrum of breast cancer pathologies, the variable suitability of DNA extracted from FFPE material and the difficulties in identifying ADJ_NT. We assessed the suitability of FFPE breast cancer material for genome-wide DNA methylation assessment of tumour and ADJ_NT.

Methods

Twenty-one archival breast tumour tissues with paired ADJ_NT obtained from separate blocks and at least 2 cm from the tumour were sourced from The Melbourne Collaborative Cohort Study (MCCS). DNA was prepared from macrodissected tissue samples and assessed for genome-wide methylation using the Infinium HumanMethylation450 Beadchip (HM450K) array.

Results

The 1000 most differentially methylated probes between tumour and ADJ_NT in this FFPE-derived dataset differentiated tumour and ADJ_NT in The Cancer Genome Atlas Network data (TCGA; derived from high molecular weight DNA using the same HM450K array).

Conclusions

Large-scale studies of genome-wide DNA methylation using FFPE breast cancer specimens offer the opportunity to further refine the pathological classification of tumours, to include subtypes that are underrepresented in the TCGA data and provide the capacity to further explore intra-tumoural heterogeneity.

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Title: Analysis of the breast cancer methylome using formalin-fixed paraffin-embedded tumour
Authors: Ee Ming Wong
JiHoon E. Joo
Catriona A. McLean
Laura Baglietto
Dallas R. English
Gianluca Severi
Hui-Chen Wu
Mary Beth Terry
John L. Hopper
Roger L. Milne
Graham G. Giles
Melissa C. Southey
Publication date: 01-11-2016
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-3971-0

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