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Linkage of Familial Wilms' Tumor Predisposition to Chromosome 19 and a Two-Locus Model for the Etiology of Familial Tumors¹

Department of Experimental Pediatrics/Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [J. M. M., L. C. S., V. H.]; Zeneca Pharmaceuticals, Wilmington, Delaware 19850 [E. C. D.]; Department of Pediatric Hematology/Oncology, Warren Clinic, Tulsa, Oklahoma 74136 [R. F.]; Department of Pediatrics, The University of Texas Health Science Center, San Antonio, Texas 78284 [C. F. G.]; Children's Hospital Medical Center of Akron, Akron, Ohio 44308-1062 [C. E. K.]; and Program in Human Molecular Biology and Genetics, University of Utah. Salt Lake City, Utah 84112 [D. V.]

Familial predisposition to Wilms' tumor (WT), a childhood kidney tumor, is inherited as an autosomal dominant trait. For most WT families studied, the 11p13 gene WT1 and genomic regions implicated in tumorigenesis in a subset of tumors can be ruled out as the site of the familial predisposition gene. Following a genome-wide genetic linkage scan, we have obtained strong evidence (log of the odds ratio = 4.0) in five families for an inherited WT predisposition gene (FWT2) at 19q13.3–q13.4. In addition, we observed loss of heterozygosity at 19q in tumors from individuals from two families in which 19q can be ruled out as the site of the inherited predisposing mutation. From these data, we hypothesize that alterations at two distinct loci are critical rate-limiting steps in the etiology of familial WTs.

¹ This work was supported by NIH Grants CA34936 and CA60114.

² To whom requests for reprints should be addressed, at Department of Experimental Pediatrics/Genetics, Box 88, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 745-0678; Fax: (713) 794-4373; E-mail: vhuff@mdacc.tmc.edu.

Received 1/16/98. Accepted 2/13/98.

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