Characterization of regions of chromosomes 12 and 16 involved in nephroblastoma tumorigenesis

✍ Scribed by Estelle Austruy; Sophie Candon; Isabelle Henry; Gabor Gyapay; Marie-France Tournade; Marcel Mannens; David Callen; Claudine Junien; Cécile Jeanpierre

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 760 KB
• Volume: 14
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870140407

✦ Synopsis

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 in 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.