title: Characterization of regions of chromosomes 12 and 16 involved in nephroblastoma tumorigenesis.
abstract: There are at least three loci involved in Wilms' tumor (WT) tumorigenesis: WT1 in 11p13, WT2 in 11p15.5, and WT3, as yet unmapped. A compilation of cytogenetic data published for 107 WT revealed that deletion of chromosome 16 and duplication of chromosome 12 occur as frequently as the well-documented 11p deletions. Allelic imbalance for chromosomes 16 and 12 was investigated in a series of 28 WT. By use of a large panel of restriction fragment length polymorphisms and (CA)n probes, we demonstrated loss of heterozygosity (LOH) for 16q in seven (25%) of the tumors. The whole length of 16q was involved in six of the tumors. Moreover, consistent with a previous report of 16q13 LOH in a sporadic WT and a constitutional breakpoint with a Beckwith-Wiedemann patient, we map a region of particular interest to between D16S308 and D16S320. The assumption that 16q LOH may be an early event was based on: 1) the detection of 16q LOH in one case of nephroblastomatosis; 2) the presence of a complete (clonal) 16q LOH in a tumor with partial (mosaic) 11p LOH; and 3) 16q LOH as the sole abnormality in one WT. By quantification of chromosome 12 allelic imbalance, we detected duplication in 18% of the total series and in 25% of the sporadic unilateral cases. The common region extended from the centromere to D12S7 in 12q21.1-q23. We also suggest that the various pathogenetically important loci are not equally involved in the different forms of WT and that their sequential involvement may differ.
authors.affiliation: INSERM U383, Université Paris V, Hôpital Necker-Enfants Malades, France.
authors.forename: E
authors.initials: E
authors.lastname: Austruy
authors.forename: S
authors.initials: S
authors.lastname: Candon
authors.forename: I
authors.initials: I
authors.lastname: Henry
authors.forename: G
authors.initials: G
authors.lastname: Gyapay
authors.forename: M F
authors.initials: MF
authors.lastname: Tournade
authors.forename: M
authors.initials: M
authors.lastname: Mannens
authors.forename: D
authors.initials: D
authors.lastname: Callen
authors.forename: C
authors.initials: C
authors.lastname: Junien
authors.forename: C
authors.initials: C
authors.lastname: Jeanpierre
mesh_terms: D000782:Aneuploidy; D002648:Child; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12; D002885:Chromosomes, Human, Pair 16; D006579:Heterozygote; D006801:Humans; D014178:Translocation, Genetic; D017624:WAGR Syndrome / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics*