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.

Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma

“…Chromosome 16q allele loss occurs in up to 25% of Wilms' tumours and has been associated with a poorer prognosis (Austruy et al, 1995;Grundy et al, 1996Grundy et al, , 1998Klamt et al, 1998;Skotnicka-Klonowicz et al, 2000). Candidate 16q Wilms' tumour suppressor genes include CDH1 and CDH13 (H-cadherin, 16q24.2-3).…”

Allelotype of pediatric rhabdomyosarcoma

“…These observations make it likely that chromosome 16q harbors a TSG which plays an important role in RMS and other tumors. Several studies in Wilms' tumor describe di erent regions on chromosome 16q which harbors the WT3 and the region of interest until now is between the chromosome bands 16q12.1-16q24.1 (Maw et al, 1992;Grundy et al, 1994;Austruy et al, 1995;Newsham et al, 1995). There might be more than one TSG located on chromosome 16q and this might explain the large region.…”

Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour

“…Thus, it is now clear that there are at least two separate loci on the short arm of chromosome 11 (in 11p13 and 11p15) which are likely to be involved in Wilms tumorigenesis (Mannens et al, 1988;1990;Coppes et al, 1992a;Reeve et al, 1989;Wadey et al, 1990). More recently, LOH along the long arm of chromosome 16 has been identi®ed in approximately 20% of tumours (Austruy et al, 1995;Coppes et al, 1992;Grundy et al, 1994;Maw et al, 1986), implicating yet another chromosome locus for WT, although in this case it appears to be involved more in progression rather than initiation, since the LOH was associated with more aggressive tumours . To complicate matters further, lack of genetic linkage between the familial form of WT and markers from either chromosome 11 or 16, in several large pedigrees, suggests that there is yet another gene which is responsible for the genesis of this subgroup of tumours (Schwartz et al, 1991;Hu et al, 1988;Grundy et al, 1988;Hu et al, 1992).…”

“…Trisomy 7 is the most common observation although deletions and translocations are also seen (Austruy et al, 1995). How genes on chromosome 7 will ®t into the picture remains to be seen since trisomy 7 usually occurs together with other chromosomal aberrations (Mitleman et al, 1991;Austruy et al, 1995;Slater and Mannens, 1992).…”