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

Dylan Z. Kelley, Emily L. Flam, Evgeny Izumchenko, Liudmila V Danilova, Hildegard A. Wulf, Theresa Guo, Dzov A. Singman, Bahman Afsari, Alyza M. Skaist, Michael Considine, Jane A. Welch, Elena Stavrovskaya, Justin A. Bishop, William H. Westra, Zubair Khan, Wayne Martin Koch, David Sidransky, Sarah Wheelan, Joseph A. Califano, Alexander Favorov & 2 others Elana Fertig, Daria Gaykalova

Research output: Contribution to journalArticle

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 (HPVþ) 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.

Original languageEnglish (US)
Pages (from-to)6538-6550
Number of pages13
JournalCancer Research
Volume77
Issue number23
DOIs
StatePublished - Dec 1 2017

Fingerprint

RNA Sequence Analysis
Chromatin Immunoprecipitation
Chromatin
Neck
Head
Genome
Neoplasms
Gene Expression
Histones
Neoplasm Genes
Human Genome
Heterografts
Carcinogenesis
RNA
Cell Line
Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Kelley, Dylan Z.; Flam, Emily L.; Izumchenko, Evgeny; Danilova, Liudmila V; Wulf, Hildegard A.; Guo, Theresa; Singman, Dzov A.; Afsari, Bahman; Skaist, Alyza M.; Considine, Michael; Welch, Jane A.; Stavrovskaya, Elena; Bishop, Justin A.; Westra, William H.; Khan, Zubair; Koch, Wayne Martin; Sidransky, David; Wheelan, Sarah; Califano, Joseph A.; Favorov, Alexander; Fertig, Elana; Gaykalova, Daria.

In: Cancer Research, Vol. 77, No. 23, 01.12.2017, p. 6538-6550.

Research output: Contribution to journalArticle

Kelley, Dylan Z. ; Flam, Emily L. ; Izumchenko, Evgeny ; Danilova, Liudmila V ; Wulf, Hildegard A. ; Guo, Theresa ; Singman, Dzov A. ; Afsari, Bahman ; Skaist, Alyza M. ; Considine, Michael ; Welch, Jane A. ; Stavrovskaya, Elena ; Bishop, Justin A. ; Westra, William H. ; Khan, Zubair ; Koch, Wayne Martin ; Sidransky, David ; Wheelan, Sarah ; Califano, Joseph A. ; Favorov, Alexander ; Fertig, Elana ; Gaykalova, Daria. / 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. In: Cancer Research. 2017 ; Vol. 77, No. 23. pp. 6538-6550.
@article{cc2debae81e54b25b16a3aa431c5b3a2,
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, {Liudmila 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 Martin} and David Sidransky and Sarah Wheelan and Califano, {Joseph A.} and Alexander Favorov and Elana Fertig and Daria Gaykalova",
year = "2017",
month = "12",
day = "1",
doi = "10.1158/0008-5472.CAN-17-0833",
language = "English (US)",
volume = "77",
pages = "6538--6550",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

TY - JOUR

T1 - 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

AU - Kelley, Dylan Z.

AU - Flam, Emily L.

AU - Izumchenko, Evgeny

AU - Danilova, Liudmila V

AU - Wulf, Hildegard A.

AU - Guo, Theresa

AU - Singman, Dzov A.

AU - Afsari, Bahman

AU - Skaist, Alyza M.

AU - Considine, Michael

AU - Welch, Jane A.

AU - Stavrovskaya, Elena

AU - Bishop, Justin A.

AU - Westra, William H.

AU - Khan, Zubair

AU - Koch, Wayne Martin

AU - Sidransky, David

AU - Wheelan, Sarah

AU - Califano, Joseph A.

AU - Favorov, Alexander

AU - Fertig, Elana

AU - Gaykalova, Daria

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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 (HPVþ) 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.

AB - 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 (HPVþ) 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.

UR - http://www.scopus.com/inward/record.url?scp=85037692264&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037692264&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-17-0833

DO - 10.1158/0008-5472.CAN-17-0833

M3 - Article

VL - 77

SP - 6538

EP - 6550

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 23

ER -