NDLI: DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status

Content Provider	Springer Nature : BioMed Central
Author	Jurmeister, Philipp Weber, Karsten Villegas, Sonia Karn, Thomas Untch, Michael Thieme, Anne Müller, Volkmar Taube, Eliane Fasching, Peter Schmitt, Wolfgang D. Marmé, Frederik Stickeler, Elmar Sinn, Bruno V. Jank, Paul Schem, Christian Klauschen, Frederick van Mackelenbergh, Marion Denkert, Carsten Loibl, Sibylle Capper, David
Abstract	Background Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1–10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup. Results In unsupervised clustering and dimensionality reduction, breast cancers with low hormone receptor expression that lacked HER2 amplification usually clustered with triple negative breast cancer (TNBC) reference samples (8/10; “LowHR TNBC-like”). In contrast, most specimens with low hormone receptor expression and HER2 amplification grouped with hormone receptor positive cancers (11/13; “LowHR HRpos-like”). We observed highly similar DNA methylation patterns of LowHR TNBC-like samples and true TNBCs. Furthermore, the Ki67 proliferation index of LowHR TNBC-like samples and clinical outcome parameters were more similar to TNBCs and differed from LowHR HRpos-like cases. Conclusions We here demonstrate that LowHR breast cancer comprises two epigenetically distinct groups. Our data strongly suggest that LowHR TNBC-like samples are molecularly, histologically and clinically closely related to TNBC, while LowHR HRpos-like specimens are closely related to hormone receptor positive tumors.
Related Links	https://clinicalepigeneticsjournal.biomedcentral.com/counter/pdf/10.1186/s13148-021-01176-5.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	18687083
DOI	10.1186/s13148-021-01176-5
Journal	Clinical Epigenetics
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2021-10-03
Access Restriction	Open
Subject Keyword	Human Genetics Gene Function
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Genetics (clinical) Developmental Biology Genetics
Journal Impact Factor	4.8/2023
5-Year Journal Impact Factor	5.8/2023

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