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A high prevalence of functional inactivation by methylation modification of p16INK4A/CDKN2/MTS1 gene in primary urothelial cancers.

Authors
  • Akao, T
  • Kakehi, Y
  • Itoh, N
  • Ozdemir, E
  • Shimizu, T
  • Tachibana, A
  • Sasaki, M S
  • Yoshida, O
Type
Published Article
Journal
Japanese journal of cancer research : Gann
Publication Date
Nov 01, 1997
Volume
88
Issue
11
Pages
1078–1086
Identifiers
PMID: 9439683
Source
Medline
License
Unknown

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.

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