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5‐Hydroxymethylcytosine as a clinical biomarker: Fluorescence‐based assay for high‐throughput epigenetic quantification in human tissues
Author(s) -
Margalit Sapir,
Avraham Sigal,
Shahal Tamar,
Michaeli Yael,
Gilat Noa,
Magod Prerna,
Caspi Michal,
Loewenstein Shelly,
Lahat Guy,
FriedmannMorvinski Dinorah,
Kariv Revital,
RosinArbesfeld Rina,
Zirkin Shahar,
Ebenstein Yuval
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32519
Subject(s) - epigenetics , 5 hydroxymethylcytosine , pancreatic cancer , biomarker , cancer , colorectal cancer , biology , computational biology , multiple myeloma , cancer research , dna methylation , medicine , bioinformatics , genetics , gene , gene expression
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.

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