Abstract
The tumor suppressor gene CDKN2 (p16/MTS1) resides on chromosome 9p21 and encodes a 16 kDa inhibitor of the cyclin-dependent kinases. Inactivation of CDKN2 by homozygous deletion, point mutation, and recently described aberrant methylation in the 5' promoter region may increase progression through the cell cycle in tumors. In this study, we examine the CDKN2 gene for the presence of inactivating alterations in human prostate cancer. Sequence analysis of cell lines revealed no mutation in LNCaP, PC3, and TSU-PR1 and a missense mutation, GAC-->TAC (asp to tyr), in exon 2 of the DU145 cell line at codon 76. No mutations were identified in three primary prostate cancers or in seven lymph node metastases. Loss of heterozygosity (LOH) was analyzed by analysis of microsatellite markers in the vicinity of the CDKN2 gene. LOH was detected in 12 (20%) of 60 primary tumors at one or more loci and in 13 (46%) of 28 metastases. Methylation analysis of the CpG-rich promoter region revealed a dense methylation of CDKN2 in cell lines PC3, PPC1, and TSU-PR1, and this was found to correlate with a lack of mRNA expression by reverse transcription-polymerase chain reaction. A demethylating agent, 5-aza-2'-deoxycytidine, induced reexpression when c...Continue Reading
Citations
Oct 16, 1999·International Journal of Cancer. Journal International Du Cancer·G PerincheryR Dahiya
Jul 24, 2001·Electrophoresis·F YamamotoH Yamanaka
Dec 10, 2002·International Journal of Cancer. Journal International Du Cancer·Dev KaranSurinder K Batra
Jun 9, 2001·The Prostate·S S StromQ Wei
Nov 3, 2010·In Vitro Cellular & Developmental Biology. Animal·Wei WeiJames G Rheinwald
Apr 11, 2001·Urology·A M De MarzoW G Nelson
Mar 4, 2000·Urology·A S Kibel, W B Isaacs
Aug 10, 2002·Cancer Letters·David F JarrardAndreas Friedl
Oct 31, 2002·Cancer Letters·Qian AnShujun Cheng
Nov 9, 2005·Prostate Cancer and Prostatic Diseases·S R J BottM Williamson
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y E WhangC L Sawyers
May 23, 2001·Journal of Medical Genetics·J F Costello, C Plass
Dec 25, 2002·Journal of Clinical Pathology·C JerónimoD Sidransky
Jul 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arnab ChakravartiUNKNOWN Radiation Therapy Oncology Group
Oct 7, 2008·BMC Cancer·Jinesh N ShahYongliang Zhao
Jun 9, 2009·BMC Cancer·Jason P W CareyJaideep Chaudhary
Aug 13, 2011·DNA and Cell Biology·Lissette Delgado-CruzataJing Shen
Jan 10, 2012·Carcinogenesis·Kwame Osei-SarfoAngel Pellicer
Jan 30, 2013·Chinese Journal of Cancer Research = Chung-kuo Yen Cheng Yen Chiu·Ahmad AmeriPedram Fadavip
Jul 13, 2002·Expert Review of Anticancer Therapy·Yehoshua GdorTimothy C Thompson
Oct 1, 2010·Kidney International·Rama S DwivediDominic S C Raj
Jul 20, 2007·The Prostate·Ananthi J AsirvathamJaideep Chaudhary
Jul 8, 2003·International Journal of Cancer. Journal International Du Cancer·Mikio YamanakaTaizo Shiraishi
Sep 2, 1999·The Journal of Thoracic and Cardiovascular Surgery·A M GroegerA Giordano
May 5, 2007·The Prostate·Shabana ShabbeerMichael A Carducci
May 10, 2005·The Prostate·Dennis FaithDavid F Jarrard
Sep 21, 2005·The Prostate·See-Tong PangGunnar Norstedt
Mar 21, 2006·Oncogene·M T McCabeM L Day
Feb 11, 2016·Oncotarget·Marco ScarpaCarlo Castoro