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

被引：54

作者：

Cejas, Paloma ^{[1
,2
,3
]}

Li, Lewyn ^{[1
,2
]}

O'Neill, Nicholas K. ^{[2
]}

Duarte, Melissa ^{[1
,2
]}

Rao, Prakash ^{[1
,2
]}

Bowden, Michaela ^{[4
]}

Zhou, Chensheng W. ^{[4
]}

Mendiola, Marta ^{[3
,5
]}

Burgos, Emilio ^{[5
]}

Feliu, Jaime ^{[3
]}

Moreno-Rubio, Juan ^{[6
]}

Guadalajara, Hector ^{[7
]}

Moreno, Victor ^{[8
]}

Garcia-Olmo, Damin ^{[7
]}

Bellmunt, Joaquim ^{[2
]}

Mullane, Stephanie ^{[2
]}

Hirsch, Michelle ^{[9
,10
]}

Sweeney, Christopher J. ^{[2
]}

Richardson, Andrea ^{[9
,10
]}

Liu, X. Shirley ^{[1
,11
,12
]}

Brown, Myles ^{[1
,2
]}

Shivdasani, Ramesh A. ^{[1
,2
]}

Long, Henry W. ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Hosp La Paz, Inst Hlth Res IdiPAZ, Dept Med Oncol, Madrid, Spain

[4] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA

[5] Hosp La Paz, Dept Pathol, Inst Hlth Res IdiPAZ, Madrid, Spain

[6] Infanta Sofia Univ Hosp, Precis Oncol Lab, Madrid, Spain

[7] Fdn Jimenez Diaz, Dept Surg, E-28040 Madrid, Spain

[8] Fdn Jimenez Diaz, Clin Res Unit, E-28040 Madrid, Spain

[9] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[12] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA

来源：

NATURE MEDICINE | 2016年 / 22卷 / 06期

关键词：

TRANSCRIPTION FACTORS; ANTIGEN RETRIEVAL; SELF-RENEWAL; GENE; IMMUNOHISTOCHEMISTRY; DIFFERENTIATION; METHYLATION; PLATFORM;

D O I：

10.1038/nm.4085

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：685 / +

页数：8

共 37 条

[1] Differential expression analysis for sequence count data [J].