16q loss of heterozygosity and microsatellite instability in Wilms' tumor

Background/Porpose: Wilms' tumor is the most common renal malignancy of chi ldhood. Loss of heterozygosity (LOH) at 16q is seen in about 17% of cases a nd has been associated with a poor prognosis. To more precisely define the pattern of 16q deletion exhibited by Wilms' tumor, the authors performed a detailed LOH analysis of 96 specimens using polymorphic microsatellite repe at markers. The authors also evaluated the neoplasms for the presence of mi crosatellite instability (MSI), Methods: A total of 96 DNA samples were studied using polymerase chain reac tion-based LOH analyses amplifying polymorphic microsatellite repeat marker s. Screening for MSI using 2 additional genetic markers also was carried ou t. Results: The authors found 16q LOH in 14 of the specimens evaluated, Compre hensive analysis of these LOH-positive specimens showed a region of loss sp anning 16p11.2-q22.1 and a separate distal region of LOH at 16q23.2-24.2. T he distal region of deletion is very small, estimated to be approximately 2 .4 megabases. In addition to the observed LOH, 2 specimens were found to co nsistently exhibit MSI, which has not been reported previously in Wilms' tu mor. Conclusions: The smallest consensus region of deletion in our analysis of W ilms' tumor 16q LOH measures 2.4 megabases at 16q23.2-q24.2. Additionally, MSI was present in a subset of tumor specimens suggesting that defects in D NA mismatch repair may contribute to the pathogenesis of Wilms' tumor. Copy right (C) 2000 by W.B. Saunders Company.