Altered trans-Activational Properties of a Mutated WT1 Gene Product in a WAGR-associated Wilms' Tumor

Seon Park, Gail Tomlinson, Perry Nisen, Daniel A. Haber

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

WAGR syndrome is an acronym for a rare constellation of congenital abnormalities including predisposition to Wilms' tumor, Aniridia, Genitourinary malformations, and mental Retardation. These congenital defects are associated with a constitutional deletion affecting one copy of chromosome band llpl3, implicating the loss of one allele from a number of contiguous genes in this syndrome. Predisposition to Wilms' tumor and genitourinary abnormalities have been attributed to hemizygosity for the WT1 tumor suppressor gene, a transcriptional repressor that is normally expressed transiently during kidney development Here we show that a Wilms' tumor arising in a child with WAGR syndrome contained a point mutation within the remaining WT1 allele. This mutation resulted in a glycine to aspartic acid substitution within the putative trans-activation domain of WT1, converting the encoded protein from a transcriptional repressor to an activator of its target DNA sequence. Thus, a critical amino acid substitution can alter the functional properties of WT1 and provide the “second hit” required for Wilms tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4757-4760
Number of pages4
JournalCancer Research
Volume53
Issue number20
StatePublished - Oct 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Altered trans-Activational Properties of a Mutated WT1 Gene Product in a WAGR-associated Wilms' Tumor'. Together they form a unique fingerprint.

Cite this