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Mutations of TP53 induce loss of DNA methylation and amplification of the TROP1 gene.

Abstract：

:p53 and DNA methylation play key roles in the maintenance of genome stability. In this work, we demonstrate that the two mechanisms are linked and that p53 plays a role in the maintenance of the DNA methylation levels. The loss of p53 was shown to induce loss of DNA methylation in the TROP1 gene, a human cancer-expressed locus that undergoes amplification when hypomethylated. This demethylation was reverted by the reintroduction of a wild-type TP53 (wtTP53) in the TP53-null cells. Using a gene-amplification assay in vivo, we demonstrate that the loss of p53 leads to a demethylation-dependent TROP1 gene amplification. The induction of gene amplification was reverted by the expression of a wtTP53 gene or by in vitro methylation of the transfected DNA with the Sss I DNA methylase. Taken together, these findings demonstrate that the inactivation of TP53 induces loss of DNA methylation and DNA methylation-dependent gene amplification.

journal_name

Oncogene

journal_title

Oncogene

authors

Nasr AF,Nutini M,Palombo B,Guerra E,Alberti S

doi

10.1038/sj.onc.1206248

subject

Has Abstract

pub_date

2003-03-20 00:00:00

pages

1668-77

issue

11

eissn

0950-9232

issn

1476-5594

pii

1206248

journal_volume

22

pub_type

杂志文章

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