Characterization of copy number alterations in a mouse model of fibrosis-associated hepatocellular carcinoma reveals concordance with human disease

Cancer Medicine
Grace ChappellIvan Rusyn

Abstract

Hepatocellular carcinoma (HCC) is a prevalent human cancer with rising incidence worldwide. Human HCC is frequently associated with chronic liver inflammation and cirrhosis, pathophysiological processes that are a consequence of chronic viral infection, disturbances in metabolism, or exposure to chemical toxicants. To better characterize the pathogenesis of HCC, we used a human disease-relevant mouse model of fibrosis-associated hepatocarcinogenesis. In this model, marked liver tumor response caused by the promutagenic chemical N-nitrosodiethylamine in the presence of liver fibrosis was associated with epigenetic events indicative of genomic instability. Therefore, we hypothesized that DNA copy number alterations (CNAs), a feature of genomic instability and a common characteristic of cancer, are concordant between human HCC and mouse models of fibrosis-associated hepatocarcinogenesis. We evaluated DNA CNAs and changes in gene expression in the mouse liver (normal, tumor, and nontumor fibrotic tissues). Additionally, we compared our findings to DNA CNAs in human HCC cases (tumor and nontumor cirrhotic/fibrotic tissues) using publicly available data from The Cancer Genome Atlas (TCGA). We observed that while fibrotic liver tissue...Continue Reading

References

Sep 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jonathan R PollackPatrick O Brown
Nov 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Martin A NowakChristoph Lengauer
Apr 19, 2003·Science·François GaudetRudolf Jaenisch
Oct 12, 2004·Biostatistics·Adam B OlshenMichael Wigler
Oct 28, 2004·Gastroenterology·Giovanna FattovichFrancesco Donato
May 27, 2005·Acta Pharmacologica Sinica·Sze-hang Lau, Xin-yuan Guan
May 28, 2005·Nature Genetics·Daniel Pinkel, Donna G Albertson
Aug 25, 2006·Nature Reviews. Cancer·Paraskevi A Farazi, Ronald A DePinho
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Jun 24, 2008·Human Mutation·Arkadiusz PiotrowskiJan P Dumanski
Jan 1, 2008·Cytogenetic and Genome Research·F SpelemanK De Preter
Sep 1, 2009·Annual Review of Genomics and Human Genetics·Feng ZhangJames R Lupski
Feb 19, 2010·Nature·Rameen BeroukhimMatthew Meyerson
Feb 23, 2010·Seminars in Liver Disease·Nelson Fausto, Jean S Campbell
Apr 14, 2010·Journal of Hepatology·Lars ZenderJosep M Llovet
Jun 25, 2010·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Jessica Zucman-Rossi
Mar 5, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kristina AleksicMichael R Speicher
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Sep 17, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Melissa M Center, Ahmedin Jemal
Feb 23, 2012·Lancet·Alejandro FornerJordi Bruix
Mar 2, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David Y Zhang, Scott L Friedman
Aug 7, 2012·Lancet·Maurice A A J van den Bosch, Luc Defreyne
Aug 7, 2012·Lancet·Roberto S OliveriChristian Gluud
Sep 26, 2012·Archives of Toxicology·Rajagopal N AravalliClifford J Steer
Dec 19, 2012·Oncogene·A Janssen, R H Medema
Jan 5, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Takeki UeharaIvan Rusyn
Mar 19, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kai WangJiangchun Xu
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Sep 21, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Charles L SawyersGeorge J Weiner
Nov 19, 2013·International Journal of Cancer. Journal International Du Cancer·Grace ChappellIgor P Pogribny
Jan 1, 2014·World Journal of Gastroenterology : WJG·De-Leung GuChian-Feng Chen
Jul 30, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ekihiro Seki, Robert F Schwabe
Sep 3, 2014·Current Protocols in Pharmacology·Takeki UeharaIvan Rusyn
Sep 13, 2014·Scientific Reports·Qing XiongTerrence S Furey
Sep 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Juliane FriemelAchim Weber
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders

❮ Previous
Next ❯

Software Mentioned

GSAASeqSP
GraphPad Prism
R package DESeq2
SWITCH
SWITCHplus
SWITCHdna
Gene Set Association Analysis for RNA Seq ( GSAASeqSP )

Related Concepts

Related Feeds

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.