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A High Prevalence of Functional Inactivation by Methylation Modification of p16INK4A/CDKN2/MTS1Gene in Primary Urothelial Cancers
- Source :
- Japanese Journal of Cancer Research : Gann
- Publication Year :
- 1997
- Publisher :
- Wiley, 1997.
-
Abstract
- We analyzed the genetic and epigenetic alterations of p16INK4A/CDKN2/MTS1 gene (MTS1 gene) in 38 primary urothelial cancers. Genetic alterations of the MTS1 gene consisted of one base substitution mutation in exon 2 (2.6%) and 6 homozygous deletions (16.2%). Hypermethylation of the 5' CpG island in exon 1 of the MTS1 gene was observed in 12 tumors (37.5%). Consequently, 19 of 38 tumors (50%) showed genetic alterations or epigenetic hypermethylation of the MTS1 gene. Retention of hypermethylated MTS1 gene(s) in 36% of the tumors showing loss of heterozygosity at the critical region indicates that the methylation modification could be an initial event followed by genomic rearrangements associated with total loss of MTS1 gene function. Immunohistochemical analysis of MTS1 expression revealed that all the tumors with genetic alterations of the MTS1 gene and 9 of 12 highly methylated tumors displayed an absence of MTS1 nuclear antigen. Genetic and epigenetic changes of the MTS1 gene were not correlated with the grade and stage of tumors, indicating that these alterations are early events in urothelial carcinogenesis, in which functional inactivation by hypermethylation is a predominant mechanism.
- Subjects :
- Urologic Neoplasms
Cancer Research
Gene Expression
Loss of Heterozygosity
Biology
medicine.disease_cause
Polymerase Chain Reaction
Article
Loss of heterozygosity
Exon
Urothelial cancer
medicine
Humans
MTS1
Kidney Pelvis
Epigenetics
Hypermethylation
Gene
Cyclin-Dependent Kinase Inhibitor p16
Polymorphism, Single-Stranded Conformational
Genetics
Ureteral Neoplasms
Point mutation
DNA, Neoplasm
Methylation
DNA Methylation
Kidney Neoplasms
Gene Expression Regulation, Neoplastic
Urinary Bladder Neoplasms
Oncology
Mutation
DNA methylation
Cancer research
Carcinogenesis
Subjects
Details
- ISSN :
- 09105050
- Volume :
- 88
- Database :
- OpenAIRE
- Journal :
- Japanese Journal of Cancer Research
- Accession number :
- edsair.doi.dedup.....0a66c1b5e6d8b269f20b3f269045520d