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

Författare:
  • Ida Johansson
  • Martin Lauss
  • Karolina Holm
  • Johan Staaf
  • Cecilia Nilsson
  • Marie-Louise Fjällskog
  • Markus Ringnér
  • Ingrid Hedenfalk
Publiceringsår: 2015
Språk: Engelska
Sidor: 1565-1579
Publikation/Tidskrift/Serie: Molecular Oncology
Volym: 9
Nummer: 8
Dokumenttyp: Artikel i tidskrift
Förlag: Elsevier

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1574-7891
Markus Ringnér
E-post: markus [dot] ringner [at] biol [dot] lu [dot] se

Forskningsingenjör

Molekylär cellbiologi

B-A317

Sölvegatan 35, Lund

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