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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Muratani, M; Deng, N; Ooi, WF; Lin, SJ; Xing, M; Xu, C; Qamra, A; Tay, ST; Malik, S; Wu, J; Lee, MH; Zhang, S; Tan, LLC; Chua, H; Wong, WK; Ong, HS; Ooi, LL; Chow, PK-H; Chan, WH; Soo, KC; Goh, LK; Rozen, S; Teh, BT; Yu, Q; Ng, HH; Tan, P

Published Date

  • January 2014

Published In

Volume / Issue

  • 5 /

Start / End Page

  • 4361 -

PubMed ID

  • 25008978

Pubmed Central ID

  • 25008978

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms5361

Language

  • eng