Epigenetic analysis of body fluids and tumor tissues: Application of a comprehensive molecular assessment for early-stage breast cancer patients

Bret Taback, Armando E. Giuliano, Ron Lai, Nora Hansen, Frederick R. Singer, Klaus Pantel, Dave S B Hoon

Research output: Chapter in Book/Report/Conference proceedingConference contribution

39 Scopus citations

Abstract

Breast cancer recurrence is a result of undetected metastasis present at the time of primary patient treatment. More sensitive methods are needed to identify subclinical disease progression to better accompany those increasing advances in early breast cancer screening. Aberrant hypermethylation of tumor-suppressor genes is found frequently in primary breast tumors and has been implicated in disease initiation and progression. Epigenetic characterization of tumor cells may provide highly specific and sensitive molecular surrogates for surveillance. We evaluated whether tumor-associated methylated DNA markers could be identified circulating in bone marrow (BM) aspirates and paired serum samples from 33 early-stage patients undergoing surgery for breast cancer. Quantitative methylation-specific PCR(qMSP) was performed using a selected tumor-related gene panel for RAR-β2, MGMT, RASSF1A, and APC. Tumor-associated hypermethylated DNA was identified in 7 (21%) of 33 BM aspirates and 9 (27%) serum samples. In three patients both BM and serum were positive for hypermethylation. The most frequently detected hypermethylation marker was RASSF1A occurring in 7 (21%) patients. Concordance was present between gene hypermethylation detected in BM or serum samples, and matched-pair primary tumors. Advanced AJCC stage was associated with an increased incidence of circulating gene hypermethylation. In addition, methylation patterns in the sentinel lymph node (SLN) metastasis corresponded with that of the primary tumor, confirming epigenetic clonality is associated with early tumor dissemination. This study demonstrates the novel finding of tumor-associated epigenetic markers in BM aspirates/blood and their potential role as targets for molecular detection.

Original languageEnglish (US)
Title of host publicationCirculating Nucleic Acids in Plasma and Serum IV
PublisherBlackwell Publishing Inc.
Pages211-221
Number of pages11
ISBN (Print)157331627X, 9781573316279
DOIs
StatePublished - Sep 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1075
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Bone marrow
  • Breast cancer
  • Methylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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