@article{ac3f750b2f194e1a998e543b70a073ee,
title = "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",
abstract = "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{\th}) 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.",
author = "Kelley, {Dylan Z.} and Flam, {Emily L.} and Evgeny Izumchenko and Danilova, {Ludmila V.} and Wulf, {Hildegard A.} and Theresa Guo and Singman, {Dzov A.} and Bahman Afsari and Skaist, {Alyza M.} and Michael Considine and Welch, {Jane A.} and Elena Stavrovskaya and Bishop, {Justin A.} and Westra, {William H.} and Zubair Khan and Koch, {Wayne M.} and David Sidransky and Wheelan, {Sarah J.} and Califano, {Joseph A.} and Favorov, {Alexander V.} and Fertig, {Elana J.} and Gaykalova, {Daria A.}",
note = "Funding Information: We thank SKCCC Next Generation Sequencing Center and JHMI Deep Sequencing & Microarray Core on performing and providing advice on ChIP-Seq and RNA-Seq data, respectively, and L. Kagohara, G. Stein-O'Brien, T. Ou, F. Zamuner, and K. Zambo for critical comments and feedback during the preparation of the manuscript. This work was supported by grants R21DE025398 (to D.A. Gaykalova), 5P50DE019032 (to D.A. Gaykalova, E.J. Fertig, D. Sidransky, W.M. Koch, and E. Izumchenko), R01CA177669 and P30CA006973 (to E.J. Fertig), R01DE023347 (to J.A. Califano), and ALCF-IASLC (to E. Izumchenko). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Funding Information: This work was supported by grants R21DE025398 (to D.A. Gaykalova), 5P50DE019032 (to D.A. Gaykalova, E.J. Fertig, D. Sidransky, W.M. Koch, and E. Izumchenko), R01CA177669 and P30CA006973 (to E.J. Fertig), R01DE023347 (to J.A. Califano), and ALCF-IASLC (to E. Izumchenko). Publisher Copyright: {\textcopyright}2017 AACR.",
year = "2017",
month = dec,
day = "1",
doi = "10.1158/0008-5472.CAN-17-0833",
language = "English (US)",
volume = "77",
pages = "6538--6550",
journal = "Cancer Research",
issn = "0008-5472",
number = "23",
}