5-Hydroxymethylcytosine as a clinical biomarker: Fluorescence-based assay for high-throughput epigenetic quantification in human tissues

Sapir Margalit, Sigal Avraham, Tamar Shahal, Yael Michaeli, Noa Gilat, Prerna Magod, Michal Caspi, Shelly Loewenstein, Guy Lahat, Dinorah Friedmann-Morvinski, Revital Kariv, Rina Rosin-Arbesfeld, Shahar Zirkin*, Yuval Ebenstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5-hydroxymethylcytosine (5-hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5-hmC quantification methods. Here we present and validate a fluorescence-based platform for high-throughput and cost-effective quantification of global genomic 5-hmC levels. We utilized the assay to characterize cancerous tissues based on their 5-hmC content, and observed a pronounced reduction in 5-hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof-of-concept data for treatment of familial adenomatous polyposis.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalInternational Journal of Cancer
Volume146
Issue number1
DOIs
StatePublished - 1 Jan 2020

Keywords

  • 5-hmC
  • 5-hydroxymethylcytosine
  • cancer
  • epigenetic biomarker
  • epigenetics
  • fluorescence

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