Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements

Masafumi Muratani, Niantao Deng, Wen Fong Ooi, Suling Joyce Lin, Manjie Xing, Chang Xu, Aditi Qamra, Su Ting Tay, Simeen Malik, Jeanie Wu, Ming Hui Lee, Shenli Zhang, Luke Lin Chuen Tan, Huihoon Chua, Wai Keong Wong, Hock Soo Ong, London Lucien Ooi, Pierce Kah-How Chow, Weng Hoong Chan, Khee Chee Soo, Liang Kee Goh, Steve Rozen, Bin Tean Teh, Qiang Yu, Huck Hui Ng and Patrick Tan ()
Additional contact information
Masafumi Muratani: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
Niantao Deng: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Wen Fong Ooi: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
Suling Joyce Lin: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
Manjie Xing: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Chang Xu: Cancer Science Institute of Singapore, National University of Singapore
Aditi Qamra: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
Su Ting Tay: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Simeen Malik: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Jeanie Wu: Cellular and Molecular Research, National Cancer Centre
Ming Hui Lee: Cellular and Molecular Research, National Cancer Centre
Shenli Zhang: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Luke Lin Chuen Tan: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Huihoon Chua: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
Wai Keong Wong: Singapore General Hospital
Hock Soo Ong: Singapore General Hospital
London Lucien Ooi: Singapore General Hospital
Pierce Kah-How Chow: Singapore General Hospital
Weng Hoong Chan: Singapore General Hospital
Khee Chee Soo: National Cancer Centre
Liang Kee Goh: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Steve Rozen: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Bin Tean Teh: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
Qiang Yu: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
Huck Hui Ng: Stem Cell and Developmental Biology, Genome Institute of Singapore
Patrick Tan: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Chromatin alterations are fundamental hallmarks of cancer. To study chromatin alterations in primary gastric adenocarcinomas, we perform nanoscale chromatin immunoprecipitation sequencing of multiple histone modifications in five gastric cancers and matched normal tissues. We identify hundreds of somatically altered promoters and predicted enhancers. Many cancer-associated promoters localize to genomic sites lacking previously annotated transcription start sites (cryptic promoters), driving expression of nearby genes involved in gastrointestinal cancer, embryonic development and tissue specification. Cancer-associated promoters overlap with embryonic stem cell regions targeted by polycomb repressive complex 2, exhibiting promoter bivalency and DNA methylation loss. We identify somatically acquired elements exhibiting germline allelic biases and non-coding somatic mutations creating new promoters. Our findings demonstrate the feasibility of profiling chromatin from solid tumours with limited tissue to identify regulatory elements, transcriptional patterns and regulatory genetic variants associated with cancer.

Date: 2014
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DOI: 10.1038/ncomms5361

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