Your browser doesn't support javascript.
loading
Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues.
Zhang, Mingfeng; Lykke-Andersen, Soren; Zhu, Bin; Xiao, Wenming; Hoskins, Jason W; Zhang, Xijun; Rost, Lauren M; Collins, Irene; Bunt, Martijn van de; Jia, Jinping; Parikh, Hemang; Zhang, Tongwu; Song, Lei; Jermusyk, Ashley; Chung, Charles C; Zhu, Bin; Zhou, Weiyin; Matters, Gail L; Kurtz, Robert C; Yeager, Meredith; Jensen, Torben Heick; Brown, Kevin M; Ongen, Halit; Bamlet, William R; Murray, Bradley A; McCarthy, Mark I; Chanock, Stephen J; Chatterjee, Nilanjan; Wolpin, Brian M; Smith, Jill P; Olson, Sara H; Petersen, Gloria M; Shi, Jianxin; Amundadottir, Laufey.
Afiliação
  • Zhang M; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Lykke-Andersen S; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
  • Zhu B; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Xiao W; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Hoskins JW; Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, FDA, Jefferson, Missouri, USA.
  • Zhang X; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Rost LM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Collins I; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, Maryland, USA.
  • Bunt MV; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Jia J; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Parikh H; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Zhang T; Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK.
  • Song L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Jermusyk A; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Chung CC; Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
  • Zhu B; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Zhou W; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Matters GL; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Kurtz RC; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Yeager M; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, Maryland, USA.
  • Jensen TH; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Brown KM; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, Maryland, USA.
  • Ongen H; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Bamlet WR; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, Maryland, USA.
  • Murray BA; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
  • McCarthy MI; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
  • Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Chatterjee N; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, Maryland, USA.
  • Wolpin BM; Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
  • Smith JP; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
  • Olson SH; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
  • Petersen GM; Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA.
  • Shi J; The Eli and Edythe L Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, Cambridge, Massachusetts, USA.
  • Amundadottir L; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Gut ; 67(3): 521-533, 2018 03.
Article em En | MEDLINE | ID: mdl-28634199
ABSTRACT

OBJECTIVE:

To elucidate the genetic architecture of gene expression in pancreatic tissues.

DESIGN:

We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison.

RESULTS:

We identified 38 615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis-eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis-eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis-eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8×10-8) and tumour-derived (p=8.3×10-5) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the 'O' mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO 'O' mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL.

CONCLUSIONS:

We have identified cis-eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pâncreas / Neoplasias Pancreáticas / Sistema ABO de Grupos Sanguíneos / RNA Neoplásico / Expressão Gênica / Locos de Características Quantitativas / Transcriptoma Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pâncreas / Neoplasias Pancreáticas / Sistema ABO de Grupos Sanguíneos / RNA Neoplásico / Expressão Gênica / Locos de Características Quantitativas / Transcriptoma Idioma: En Ano de publicação: 2018 Tipo de documento: Article