Document Detail


Methylation and mutational analysis of p27(kip1) in prostate carcinoma.
MedLine Citation:
PMID:  11536304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We have previously identified 12p12-13 as a region of frequent genetic loss in prostate carcinoma. A candidate tumor suppressor gene at this locus is the cyclin dependent kinase inhibitor p27(kip1), which has been implicated as a marker of aggressive prostate carcinoma. Herein, we examine metastatic prostate tumors, xenografts, and cell lines for gene inactivation via mutational inactivation or promoter hypermethylation. METHODS: Mutation analysis was performed on metastatic prostate tumors of 18 patients, eight prostate carcinoma cell lines, and 18 xenografts by PCR amplification of the entire open reading frame of p27(kip1). PCR products were sequenced directly using internal primers. Methylation analysis was performed on four cell lines and nine xenografts using direct sequencing of cloned PCR products of bisulfite treated DNA. Presence of a CpG was consistent with methylation of that cytosine in the original sample. RESULTS: With the exception of the previously reported homozygous deletion, no additional mutations were identified. Methylated CpG residues were identified in three xenografts (LuCAP23, LuCAP35, and PC82) and the methylated residues clustered at six sites; the cytosines 69, 149, 191, 286, 349, and 487 base pairs 5' of the ATG start codon. However, no sample demonstrated promotor methylation in all sequenced clones and the number of methylated base pairs ranged from seven to three, not the level usually associated with gene silencing. CONCLUSIONS: Mutational inactivation of p27(kip1) is a rare event in metastatic prostate carcinoma. While CpG methylation does occur, it is an infrequent event and does not appear to be the mechanism of p27(kip1) down regulation in prostate carcinoma.
Authors:
A S Kibel; M Christopher; D A Faith; G S Bova; P J Goodfellow; W B Isaacs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Prostate     Volume:  48     ISSN:  0270-4137     ISO Abbreviation:  Prostate     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-09-05     Completed Date:  2001-10-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  248-53     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Affiliation:
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63105, USA. kibela@msnotes.wustl.edu
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle Proteins / genetics*
Cyclin-Dependent Kinase Inhibitor p27
DNA Methylation*
DNA, Neoplasm / genetics,  metabolism
Gene Expression Regulation, Neoplastic
Gene Silencing
Genes, cdc
Humans
Male
Mutation
Prostatic Neoplasms / genetics*,  metabolism
Sequence Analysis, DNA
Tumor Cells, Cultured
Tumor Suppressor Proteins*
Grant Support
ID/Acronym/Agency:
CA 58236/CA/NCI NIH HHS; CA 59457/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA, Neoplasm; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27

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