Format

Send to

Choose Destination
Nat Med. 2016 Jun;22(6):685-91. doi: 10.1038/nm.4085. Epub 2016 Apr 25.

Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.

Author information

1
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
2
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
3
Department of Medical Oncology, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.
4
Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
5
Department of Pathology, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.
6
Precision Oncology Laboratory, Infanta Sofia University Hospital, Madrid, Spain.
7
Department of Surgery, Jimenez Diaz Foundation, Madrid, Spain.
8
Clinical Research Unit, Jimenez Diaz Foundation, Madrid, Spain.
9
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
10
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts, USA.

Abstract

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 chromatin-state 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.

PMID:
27111282
DOI:
10.1038/nm.4085
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center