title: Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
abstract: BACKGROUND
  Epigenetic modifications such as aberrant DNA methylation has long been associated with tumorogenesis. Little is known, however, about how these modifications appear in cancer progression. Comparing the methylome of breast carcinomas and locoregional evolutions could shed light on this process.
  
  
  METHODS
  The methylome profiles of 48 primary breast carcinomas (PT) and their matched axillary metastases (PT/AM pairs, 20 cases), local recurrences (PT/LR pairs, 17 cases) or contralateral breast carcinomas (PT/CL pairs, 11 cases) were analyzed. Univariate and multivariate analyzes were performed to determine differentially methylated probes (DMPs), and a similarity score was defined to compare methylation profiles. Correlation with copy-number based score was calculated and metastatic-free survival was compared between methods.
  
  
  RESULTS
  49 DMPs were found for the PT/AM set, but none for the others (FDR < 5%). Hierarchical clustering clustered 75% of the PT/AM, 47% of the PT/LR, and none of the PT/CL pairs together. A methylation-based score (MS) was defined as a clonality measure. The PT/AM set contained a high proportion of clonal pairs while PT/LR pairs were evenly split between high and low MS score, suggesting two groups: true recurrences (TR) and new primary tumors (NP). CL were classified as new tumors. MS score was significantly correlated with copy-number based scores. There was no significant difference between the metastatic-free survival of groups of patients based on different classifications.
  
  
  CONCLUSIONS
  Epigenomic alterations are well suited to study clonality and track cancer progression. Methylation-based classification of TR and NP performed as well as clinical and copy-number based methods suggesting that these phenomenons are tightly linked.
authors.affiliation: Centre for Computational Biology, Mines ParisTech, Fontainebleau, France; Institut Curie, Paris, France; U900, INSERM, Paris, France.
authors.forename: Matahi
authors.initials: M
authors.lastname: Moarii
authors.affiliation: UMR144, Oncology Molecular Team, Institut Curie, Paris, France; Department of translational research, Residual Tumor and Response to Treatment Team, Institut Curie, Paris, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Pinheiro
authors.affiliation: Department of Tumor Biology, Institut Curie, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.affiliation: Department of Radiotherapy, Institut Curie, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.affiliation: Department of Tumor Biology, Institut Curie, Paris, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Caly
authors.affiliation: Centre for Computational Biology, Mines ParisTech, Fontainebleau, France; Institut Curie, Paris, France; U900, INSERM, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: Centre for Computational Biology, Mines ParisTech, Fontainebleau, France; Institut Curie, Paris, France; U900, INSERM, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Stoven
authors.affiliation: Centre for Computational Biology, Mines ParisTech, Fontainebleau, France; Institut Curie, Paris, France; U900, INSERM, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vert
authors.affiliation: UMR144, Oncology Molecular Team, Institut Curie, Paris, France; Department of translational research, Residual Tumor and Response to Treatment Team, Institut Curie, Paris, France; Department of Surgery, Institut Curie, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm
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