Methylation profiling of ductal carcinoma in situ and its relationship to histopathological features

DNA methylation is a well-studied biomarker in invasive breast cancer, but its role in ductal carcinoma in situ (DCIS) is less well characterized. The aims of this study are to assess the methylation profile in DCIS for a panel of well-characterized genes that are frequently methylated in breast can...

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Published in:Breast cancer research : BCR 2014-01, Vol.16 (5), p.423-423
Main Authors: Pang, Jia-Min B, Deb, Siddhartha, Takano, Elena A, Byrne, David J, Jene, Nicholas, Boulghourjian, Alice, Holliday, Anne, Millar, Ewan, Lee, C Soon, O'Toole, Sandra A, Dobrovic, Alexander, Fox, Stephen B
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Carcinoma, Intraductal, Noninfiltrating - genetics
Carcinoma, Intraductal, Noninfiltrating - pathology
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Phenotype
Promoter Regions, Genetic
Sequence Analysis, DNA
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Summary:DNA methylation is a well-studied biomarker in invasive breast cancer, but its role in ductal carcinoma in situ (DCIS) is less well characterized. The aims of this study are to assess the methylation profile in DCIS for a panel of well-characterized genes that are frequently methylated in breast cancer, to investigate the relationship of methylation with pathological features, and to perform a proof-of-principle study to evaluate the practicality of methylation as a biomarker in diagnostic DCIS material. Promoter CpG island methylation for a panel of 11 breast cancer-related genes was performed by methylation-sensitive high resolution melting (MS-HRM). Formalin-fixed, paraffin-embedded (FFPE) biopsies from 72 samples of pure DCIS (DCIS occurring in the absence of synchronous invasive carcinoma), 10 samples of mixed DCIS (DCIS adjacent to invasive carcinoma), and 18 samples of normal breast epithelium adjacent to a DCIS lesion were micro-dissected prior to DNA extraction. Methylation was seen for all the tested genes except BRCA1. RASSF1A was the most frequently methylated gene (90% of DCIS samples) and its methylation was associated with comedo necrosis (p = 0.018). Cluster analysis based on the methylation profile revealed four groups, the highly methylated cluster being significantly associated with high nuclear grade, HER2 amplification, negative estrogen receptor (ER) α status, and negative progesterone receptor (PgR) status, (p = 0.038, p = 0.018, p
ISSN:1465-5411
1465-542X
DOI:10.1186/s13058-014-0423-9