Remodeling of the methylation landscape in breast cancer metastasis Journal Article


Authors: Reyngold, M.; Turcan, S.; Giri, D.; Kannan, K.; Walsh, L. A.; Viale, A.; Drobnjak, M.; Vahdat, L. T.; Lee, W.; Chan, T. A.
Article Title: Remodeling of the methylation landscape in breast cancer metastasis
Abstract: The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI)-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process. © 2014 Reyngold et al.
Keywords: clinical article; controlled study; primary tumor; gene sequence; promoter region; lymph node metastasis; disease association; gene expression profiling; genetic association; dna methylation; gene expression regulation; cpg island; gene identification; dna flanking region; breast metastasis; transcriptome; regional metastasis; nuclear reprogramming; genetic heterogeneity; human; article
Journal Title: PLoS ONE
Volume: 9
Issue: 8
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2014-08-01
Start Page: e103896
Language: English
DOI: 10.1371/journal.pone.0103896
PROVIDER: scopus
PMCID: PMC4118917
PUBMED: 25083786
DOI/URL:
Notes: Export Date: 2 September 2014 -- CODEN: POLNC -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    317 Chan
  2. Dilip D Giri
    184 Giri
  3. Marsha Reyngold
    104 Reyngold
  4. Agnes Viale
    245 Viale
  5. Sevin Turcan
    25 Turcan
  6. Logan Alexander Walsh
    19 Walsh
  7. Kasthuri Srinivasan Kannan
    11 Kannan
  8. William Lee
    39 Lee