Abstract

A revised application to test the hypothesis that tumorigenesis in Wilms tumor results from mutations, either germline or somatic, at more than one locus in the tumor cell. One Wilms tumor gene is known: the transcription factor WT1 on chromosome 11p. The PI proposes to fine map a second locus, WT2, for hereditary Wilms tumor on chr19q and identify the responsible gene.
Specific Aims are: (1) Ascertain and sample additional families with familial WT; (2) identify the subset that show linkage to 19q (as well as any families linked to other regions implicated in WT); (3) explore all familial cases, whether linked to 19q or not, for LOH involving the critical region on 19q or other regions implicated in WT; (4) refine the position of the 19q WT2 locus on a physical map of the region using meiotic recombination, loss of heterozygosity, and disequilibrium approaches; and (5) screen candidate genes and ESTs in the region for germline and somatic mutations in WT patients

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA078257-04
Application #
6513249
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Seminara, Daniela
Project Start
1999-05-01
Project End
2004-02-29
Budget Start
2002-04-01
Budget End
2003-02-28
Support Year
4
Fiscal Year
2002
Total Cost
$362,880
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Pediatrics
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Gao, Fei; Maiti, Sourindra; Alam, Nargis et al. (2006) The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A 103:11987-92
Ruteshouser, E Cristy; Hendrickson, Brett W; Colella, Stefano et al. (2005) Genome-wide loss of heterozygosity analysis of WT1-wild-type and WT1-mutant Wilms tumors. Genes Chromosomes Cancer 43:172-80
Royer-Pokora, Brigitte; Beier, Manfred; Henzler, Markus et al. (2004) Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am J Med Genet A 127A:249-57
Gao, Fei; Maiti, Sourindra; Sun, Guizhi et al. (2004) The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. Mol Cell Biol 24:9899-910
Udtha, Malini; Lee, Sang-Joon; Alam, Rita et al. (2003) Upregulation of c-MYC in WT1-mutant tumors: assessment of WT1 putative transcriptional targets using cDNA microarray expression profiling of genetically defined Wilms' tumors. Oncogene 22:3821-6
Yin, Xiaoying; Grove, Linnette; Rogulski, Kenneth et al. (2002) Myc target in myeloid cells-1, a novel c-Myc target, recapitulates multiple c-Myc phenotypes. J Biol Chem 277:19998-20010
Dharnidharka, V R; Ruteshouser, E C; Rosen, S et al. (2001) Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in twins. Pediatr Nephrol 16:227-31
Ruteshouser, E C; Ashworth, L K; Huff, V (2001) Absence of PPP2R1A mutations in Wilms tumor. Oncogene 20:2050-4
Maiti, S; Alam, R; Amos, C I et al. (2000) Frequent association of beta-catenin and WT1 mutations in Wilms tumors. Cancer Res 60:6288-92