title: The CpG island methylator phenotype in breast cancer is associated with the lobular subtype.
abstract: BACKGROUND
  Aberrations in DNA methylation patterns are well-described in human malignancies. However, the existence of the 'CpG island methylator phenotype' (CIMP) in human breast cancer is still controversial.
  
  
  METHODS
  Illumina's HumanMethylation 450K BeadChip was used to analyze genome-wide DNA methylation patterns. Chromosomal abnormalities were determined by array-based CGH.
  
  
  RESULTS
  Invasive lobular breast carcinomas exhibit the highest number of differentially methylated CpG sites and a strong inverse correlation of aberrant DNA hypermethylation and copy number alterations. Nine differentially methylated regions within seven genes discriminating the investigated subgroups were identified and validated in an independent validation cohort and correlated to a better relapse-free survival.
  
  
  CONCLUSIONS
  These results depict a clear difference between genetically and epigenetically unstable breast carcinomas indicating different ways of tumor progression and/or initiation, which strongly supports the association of CIMP with the lobular subtype and provide new options for detection and therapy.
authors.affiliation: Institute of Pathology, Hannover Medical School, Carl-Neuber-Str. 1, D-30625 Hannover, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Roessler
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: Jana
authors.initials: J
authors.lastname: Gutwein
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Veronika
authors.initials: V
authors.lastname: Weyer
authors.forename: Murat
authors.initials: M
authors.lastname: Sariyar
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Rita
authors.initials: R
authors.lastname: Schmutzler
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Tilman
authors.initials: T
authors.lastname: Heinrich
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abbas
authors.forename: Wiebke
authors.initials: W
authors.lastname: Antonopoulos
authors.forename: Elisa
authors.initials: E
authors.lastname: Schipper
authors.forename: Britta
authors.initials: B
authors.lastname: Hasemeier
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D006801:Humans; D010641:Phenotype
keywords: CpG island methylator phenotype; DNA methylation; breast cancer; epigenetics; lobular breast cancer