Integrated Analysis of Whole-Genome ChIP-Seq and RNA-Seq Data of Primary Head and Neck Tumor Samples Associates HPV Integration Sites with Open Chromatin Marks.

Autor:	Kelley DZ; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Flam EL; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Izumchenko E; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Danilova LV; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Laboratory of Systems Biology and Computational Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia., Wulf HA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Guo T; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Singman DA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Afsari B; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Skaist AM; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Considine M; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Welch JA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Pathology, Johns Hopkins Medical School of Medicine, Baltimore, Maryland., Stavrovskaya E; Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.; Institute for Information Transmission Problems, RAS, Moscow, Russia., Bishop JA; Department of Pathology, Johns Hopkins Medical School of Medicine, Baltimore, Maryland., Westra WH; Department of Pathology, Johns Hopkins Medical School of Medicine, Baltimore, Maryland., Khan Z; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Koch WM; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Sidransky D; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Wheelan SJ; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Califano JA; Head and Neck Cancer Center, Moores Cancer Center, University of California, San Diego, La Jolla, California.; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, La Jolla, California., Favorov AV; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Laboratory of Systems Biology and Computational Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.; Laboratory of Bioinformatics, Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russia., Fertig EJ; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Gaykalova DA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. dgaykal1@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2017 Dec 01; Vol. 77 (23), pp. 6538-6550. Date of Electronic Publication: 2017 Sep 25.
DOI:	10.1158/0008-5472.CAN-17-0833
Abstrakt:	Chromatin alterations mediate mutations and gene expression changes in cancer. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has been utilized to study genome-wide chromatin structure in human cancer cell lines, yet numerous technical challenges limit comparable analyses in primary tumors. Here we have developed a new whole-genome analytic pipeline to optimize ChIP-Seq protocols on patient-derived xenografts from human papillomavirus-related (HPV + ) head and neck squamous cell carcinoma (HNSCC) samples. We further associated chromatin aberrations with gene expression changes from a larger cohort of the tumor and normal samples with RNA-Seq data. We detect differential histone enrichment associated with tumor-specific gene expression variation, sites of HPV integration in the human genome, and HPV-associated histone enrichment sites upstream of cancer driver genes, which play central roles in cancer-associated pathways. These comprehensive analyses enable unprecedented characterization of the complex network of molecular changes resulting from chromatin alterations that drive HPV-related tumorigenesis. Cancer Res; 77(23); 6538-50. ©2017 AACR . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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