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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

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, Patrick Tan

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. More... »

PAGES

4361

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms5361

    DOI

    http://dx.doi.org/10.1038/ncomms5361

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1020706717

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25008978


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