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

Author

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  • Masafumi Muratani

    (Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
    Present address: Department of Genome Biology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan)

  • Niantao Deng

    (Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
    NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore)

  • 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
    NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore)

  • Chang Xu

    (Cancer Science Institute of Singapore, National University of Singapore)

  • Aditi Qamra

    (Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Su Ting Tay

    (Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
    Cellular and Molecular Research, National Cancer Centre)

  • 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
    National Cancer Centre
    Office of Clinical Sciences, Duke-NUS Graduate Medical School)

  • 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
    Cancer Science Institute of Singapore, National University of Singapore
    Laboratory of Cancer Epigenome, National Cancer Centre)

  • 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
    Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School
    Cancer Science Institute of Singapore, National University of Singapore
    Cellular and Molecular Research, National Cancer Centre)

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.

Suggested Citation

  • 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 & , 2014. "Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5361
    DOI: 10.1038/ncomms5361
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    Cited by:

    1. Mihoko Saito-Adachi & Natsuko Hama & Yasushi Totoki & Hiromi Nakamura & Yasuhito Arai & Fumie Hosoda & Hirofumi Rokutan & Shinichi Yachida & Mamoru Kato & Akihiko Fukagawa & Tatsuhiro Shibata, 2023. "Oncogenic structural aberration landscape in gastric cancer genomes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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