DNA methylation in breast cancers: Differences based on estrogen receptor status and recurrence

Abstract

DNA methylation plays a role in the etiology of primary breast cancers. We analyzed paired primary and second breast tumors to elucidate the role of methylation in recurrence. Methylation profiles from paired primary and second breast tumors of 23 women were assessed using the HumanMethylation450 BeadChip. Twelve women had estrogen receptor positive (ERpos) primary and second tumors, five had estrogen receptor negative (ERneg) primary and second tumors, and six had an ERpos primary tumor but an ERneg second tumor. Stratifying tumors by occurrence revealed that the greater methylation previously associated with ERpos tumors, is more pronounced in primary tumors than in second tumors. Further, ERneg second tumors are more methylated than ERpos second tumors among women who had ERpos primary tumors. Pathway analyses using gene lists generated from comparisons of methylation in ERpos primary tumors from the paired sets with ERpos tumors from six women without recurrences, identified differences between groups based on the ER status of the second tumor. Hypermethylated genes of significantly enriched pathways were differentially associated with survival. DNA methylation profiles of ERpos primary breast tumors support the development and use of tumor methylation profiles for stratifying women with breast cancer both for prognosis and therapy.

Document Details

Document Type
Pub Defense Publication
Publication Date
Sep 19, 2018
Source ID
10.1002/jcb.27431

Entities

People

  • Brian T. Pentecost
  • Christopher N. Otis
  • Kathleen F. Arcaro
  • Kristin E Williams
  • Rahul M. Jawale
  • Sallie S. Schneider

Organizations

  • Baystate Health
  • Congressionally Directed Medical Research Programs
  • University of Massachusetts Amherst
  • Wadsworth Center

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Readers

  • Molecular and genetic basis of cancer.
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.