Skip to Main content Skip to Navigation
Journal articles

Epigenomic Alterations in Breast Carcinoma from Primary Tumor to Locoregional Recurrences

Abstract : Introduction: 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. Conclusion: 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.
Complete list of metadata

Cited literature [46 references]  Display  Hide  Download

https://hal-mines-paristech.archives-ouvertes.fr/hal-01064211
Contributor : Bibliothèque Mines Paristech <>
Submitted on : Monday, September 15, 2014 - 5:39:45 PM
Last modification on : Tuesday, December 8, 2020 - 3:38:39 AM
Long-term archiving on: : Tuesday, December 16, 2014 - 11:40:33 AM

File

journal.pone.0103986.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Matahi Moarii, Alice Pinheiro, Brigitte Sigal-Zafrani, Alain Fourquet, Martial Caly, et al.. Epigenomic Alterations in Breast Carcinoma from Primary Tumor to Locoregional Recurrences. PLoS ONE, Public Library of Science, 2014, 9 (8), pp.e103986. ⟨10.1371/journal.pone.0103986⟩. ⟨hal-01064211⟩

Share

Metrics

Record views

1055

Files downloads

902