期刊
NATURE MEDICINE
卷 22, 期 6, 页码 685-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nm.4085
关键词
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资金
- DFCI-Novartis Drug Discovery Program
- US NIH [P50CA127003]
- Susan F. Smith Center for Women's Cancers
- Susan G. Komen foundation
- Breast Cancer Research foundation
- Medical Oncology Translational Grant Program from Dana-Farber Cancer Institute
- Instituto de Salud Carlos III the Spanish Economy and Competitiveness Ministry [PI13-01818]
- ConSEPOC-Comunidad de Madrid [S2010/BMD-2542]
- Asociacion Espanola Contra el Cancer (Programa de Formacion Avanzada en Oncologia)
- Fundacion Caja Madrid
Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatinstate maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.
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