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Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes.

Johansson, Ida LU ; Lauss, Martin LU ; Holm, Karolina LU ; Staaf, Johan LU ; Nilsson, Cecilia; Fjällskog, Marie-Louise; Ringnér, Markus LU and Hedenfalk, Ingrid LU (2015) In Molecular Oncology 9(8). p.1565-1579
Abstract
Male breast cancer (MBC) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and... (More)
Male breast cancer (MBC) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 target genes and high expression of EZH2, one of the core components of PRC2. Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster. The majority of the MBC tumors remained grouped together within the clusters rather than being interspersed among the FBC tumors. Differences in the genomic location of methylated CpGs, as well as in the regulation of central canonical pathways may explain the separation between MBC and FBC tumors in the respective clusters. These findings further suggest that MBC is not readily defined using conventional criteria applied to FBC. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Molecular Oncology
volume
9
issue
8
pages
1565 - 1579
publisher
Elsevier
external identifiers
  • pmid:25990542
  • wos:000362308500006
  • scopus:84942193244
ISSN
1574-7891
DOI
10.1016/j.molonc.2015.04.013
language
English
LU publication?
yes
id
61c99be9-819a-4051-9bf6-2daf6b6b9e1c (old id 5448597)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25990542?dopt=Abstract
date added to LUP
2015-06-05 00:31:49
date last changed
2017-10-01 03:14:13
@article{61c99be9-819a-4051-9bf6-2daf6b6b9e1c,
  abstract     = {Male breast cancer (MBC) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 target genes and high expression of EZH2, one of the core components of PRC2. Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster. The majority of the MBC tumors remained grouped together within the clusters rather than being interspersed among the FBC tumors. Differences in the genomic location of methylated CpGs, as well as in the regulation of central canonical pathways may explain the separation between MBC and FBC tumors in the respective clusters. These findings further suggest that MBC is not readily defined using conventional criteria applied to FBC.},
  author       = {Johansson, Ida and Lauss, Martin and Holm, Karolina and Staaf, Johan and Nilsson, Cecilia and Fjällskog, Marie-Louise and Ringnér, Markus and Hedenfalk, Ingrid},
  issn         = {1574-7891},
  language     = {eng},
  number       = {8},
  pages        = {1565--1579},
  publisher    = {Elsevier},
  series       = {Molecular Oncology},
  title        = {Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes.},
  url          = {http://dx.doi.org/10.1016/j.molonc.2015.04.013},
  volume       = {9},
  year         = {2015},
}