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 (ADJNT). 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 ADJNT. We assessed the suitability of FFPE breast cancer material for genome-wide DNA methylation assessment of tumour and ADJNT. METHODS:Twenty-one archival breast tumour tissues with paired ADJNT 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 ADJNT in this FFPE-derived dataset differentiated tumour and ADJNT 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.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Wong EM,Joo JE,McLean CA,Baglietto L,English DR,Severi G,Wu HC,Terry MB,Hopper JL,Milne RL,Giles GG,Southey MCdoi
10.1007/s10549-016-3971-0subject
Has Abstractpub_date
2016-11-01 00:00:00pages
173-180issue
1eissn
0167-6806issn
1573-7217pii
10.1007/s10549-016-3971-0journal_volume
160pub_type
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