Identification of a minimal region of loss on the short arm of chromosome 1 in Wilms tumor.

We have analyzed the short arm of chromosome 1 using loss of heterozygosity (LOH) analysis in Wilms tumors (WT) to identify a minimal region of loss. 1909 WT, 22 malignant rhabdoid tumors of the kidney and 90 clear cell carcinomas of the kidney (CCSK) were subjected to LOH analysis using five markers flanked by D1S243 and D1S244. 225 WT and 4 CCSK displayed LOH for this region. A group of 16 cases which had lost heterozygosity for at least one locus but also retained heterozygosity for at least one locus within this region were more finely analyzed using a panel of 24 microsatellite markers. A minimum region of loss located between D1S2694 and D1S244 spanning an area of 3.23 Mb was found in 15/16 of these tumors. No evidence for a second locus within this region was identified. This region of loss overlaps that found in neuroblastoma and harbors candidate genes highly expressed in fetal kidney i.e., LZIC, ICAT, and DNB5. Denaturing HPLC and quantitative RT-PCR analysis of these three genes, however, revealed no aberrations in WT samples retaining heterozygosity (8 cases) or displaying LOH 1p (8 cases). Further studies are required to identify the presumed tumor suppressor gene located within this region of 1p.