title: Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements.
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.
authors.affiliation: 1] Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore [2].
authors.forename: Masafumi
authors.initials: M
authors.lastname: Muratani
authors.affiliation: 1] Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore [2] NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
authors.forename: Niantao
authors.initials: N
authors.lastname: Deng
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
authors.forename: Wen Fong
authors.initials: WF
authors.lastname: Ooi
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
authors.forename: Suling Joyce
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: 1] Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore [2] NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
authors.forename: Manjie
authors.initials: M
authors.lastname: Xing
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore.
authors.forename: Chang
authors.initials: C
authors.lastname: Xu
authors.affiliation: 1] Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore [2] Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive #04-01, Singapore 117597, Singapore.
authors.forename: Aditi
authors.initials: A
authors.lastname: Qamra
authors.affiliation: 1] Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore [2] Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Su Ting
authors.initials: ST
authors.lastname: Tay
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Simeen
authors.initials: S
authors.lastname: Malik
authors.affiliation: Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Jeanie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Ming Hui
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Shenli
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Luke Lin Chuen
authors.initials: LL
authors.lastname: Tan
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
authors.forename: Huihoon
authors.initials: H
authors.lastname: Chua
authors.affiliation: Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
authors.forename: Wai Keong
authors.initials: WK
authors.lastname: Wong
authors.affiliation: Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
authors.forename: Hock Soo
authors.initials: HS
authors.lastname: Ong
authors.affiliation: Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
authors.forename: London Lucien
authors.initials: LL
authors.lastname: Ooi
authors.affiliation: 1] Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore [2] Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore [3] Office of Clinical Sciences, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Pierce Kah-How
authors.initials: PK
authors.lastname: Chow
authors.affiliation: Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
authors.forename: Weng Hoong
authors.initials: WH
authors.lastname: Chan
authors.affiliation: Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Khee Chee
authors.initials: KC
authors.lastname: Soo
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Liang Kee
authors.initials: LK
authors.lastname: Goh
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.affiliation: 1] Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore [2] Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore [3] Laboratory of Cancer Epigenome, Department of Medical Sciences, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
authors.forename: Huck Hui
authors.initials: HH
authors.lastname: Ng
authors.affiliation: 1] Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore [2] Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore [3] Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore [4] Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D016022:Case-Control Studies; D002843:Chromatin / Q000235:genetics*; D004247:DNA / Q000235:genetics; D016172:DNA Fingerprinting / Q000379:methods*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D036103:Nanotechnology / Q000379:methods*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D024363:Transcription Initiation Site
chemical_list: D002843:Chromatin; D004273:DNA, Neoplasm; D006657:Histones; D004247:DNA