NORE1B, a candidate tumor suppressor, is epigenetically silenced in human hepatocellular carcinoma

Journal of Hepatology
Doris MacheinerBettina Grasl-Kraupp

Abstract

In human hepatocellular carcinoma (HCC) the ras-proto-oncogene is rarely mutated. We therefore studied the possible inactivation of the putative tumor-suppressors and ras-associating proteins, NORE1A, NORE1B, and RASSF1A in HCCs by mutation or epigenetic gene silencing through promoter-CpG hypermethylation. SSCP-analyses, sequencing, and methylation-specific PCR were performed in 28 fibrotic/cirrhotic livers and 40 HCCs. The sequence of NORE1A/B exhibited no deviations and that of the RASSF1A gene a non-silent polymorphism ( approximately 10% of cases) and a missense mutation (one HCC). Both alterations may affect the growth-inhibiting capability of RASSF1A. Epigenetic inactivation of NORE1B was found in 62% of the HCCs and in hepatocarcinoma-cell lines due to considerable promoter-methylation of the gene. Methylation was detected also for RASSF1A in HCCs and hepatocarcinoma cell-lines. As a result, 97% of the HCCs revealed epigenetic silencing of NORE1B, RASSF1A, or both. In contrast every third fibrotic/cirrhotic liver only exhibited silencing of one or both genes. The candidate tumor suppressor genes NORE1B and RASSF1A are epigenetically down-regulated alone in at least 62%, or in combination in 97% of the HCCs studied. This...Continue Reading

References

Sep 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·UNKNOWN International Working Party
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
Feb 25, 1998·Japanese Journal of Cancer Research : Gann·L SunS Hirohashi
Nov 25, 2000·Cellular and Molecular Life Sciences : CMLS·P Crespo, J León
May 3, 2001·Journal of the National Cancer Institute·D G BurbeeJ D Minna
Feb 28, 2002·Current Biology : CB·Andrei KhokhlatchevJoseph Avruch
May 25, 2002·Molecular and Cellular Biology·Latha ShivakumarMichael A White
Nov 9, 2002·Bioinformatics·Long-Cheng Li, Rajvir Dahiya
Mar 28, 2003·Oncogene·Undraga SchagdarsurenginReinhard Dammann
Sep 26, 2003·The American Journal of Pathology·Sun LeeGyeong Hoon Kang
Dec 10, 2003·Oncogene·Adrienne D Cox, Channing J Der
Mar 10, 2004·Oncogene·Yumi AoyamaXian-Feng Zhang
Mar 20, 2004·Journal of Hepatology·Maria RaidlBettina Grasl-Kraupp
May 4, 2004·Nature Reviews. Molecular Cell Biology·Mathew L ColemanMichael F Olson

❮ Previous
Next ❯

Citations

Aug 21, 2013·Advances in Biological Regulation·Jia Jia Chan, Matilda Katan
Dec 16, 2011·Journal of Gastroenterology and Hepatology·Xiaojing ZhangYanqing Ding
Apr 27, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bert H O'NeilDaniel M Sullivan
Mar 20, 2008·World Journal of Gastroenterology : WJG·Alev DeliMichael Grusch
Mar 20, 2008·World Journal of Gastroenterology : WJG·Juliette Martin, Jean-Francois Dufour
Feb 25, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Li-Li LiuChris Zhiyi Zhang
Sep 11, 2014·Pharmacology & Therapeutics·Ioannis AnestopoulosMihalis I Panayiotidis
Jun 10, 2015·Biochemical and Biophysical Research Communications·Takataro FukuharaTatsuo Kinashi
Apr 3, 2015·European Journal of Clinical Investigation·Bénédicte Delire, Peter Stärkel
Apr 7, 2009·Biochimica Et Biophysica Acta·Antje M RichterReinhard H Dammann
Aug 19, 2007·Biochimica Et Biophysica Acta·Louise van der Weyden, David J Adams
Sep 17, 2013·Molecular and Cellular Endocrinology·Yunli ZhouAnne Klibanski
May 2, 2012·Molecular Biology International·Diego F CalvisiFrank Dombrowski
Jan 22, 2018·Cellular and Molecular Life Sciences : CMLS·Hiroaki IwasaYutaka Hata
Jul 3, 2008·British Journal of Cancer·S SagmeisterB Grasl-Kraupp
Nov 26, 2010·British Journal of Cancer·J AvruchN Bardeesy
Nov 21, 2013·Cancers·Antje M RichterReinhard H Dammann
Nov 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bin LuYajun Guo
Jan 2, 2009·Cancer Research·Doris MacheinerBettina Grasl-Kraupp
Dec 14, 2019·Genes & Diseases·Mohammad Reza ZinatizadehSeyed Rouhollah Miri
Sep 20, 2007·Journal of Cell Science·Howard DonningerGeoffrey J Clark

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

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

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.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

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.