PLoS ONE (Jan 2014)

Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.

  • Matahi Moarii,
  • Alice Pinheiro,
  • Brigitte Sigal-Zafrani,
  • Alain Fourquet,
  • Martial Caly,
  • Nicolas Servant,
  • Véronique Stoven,
  • Jean-Philippe Vert,
  • Fabien Reyal

DOI
https://doi.org/10.1371/journal.pone.0103986
Journal volume & issue
Vol. 9, no. 8
p. e103986

Abstract

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IntroductionEpigenetic 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.MethodsThe 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.Results49 DMPs were found for the PT/AM set, but none for the others (FDR ConclusionEpigenomic 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.