Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours.
In this paper we describe the analysis of genetic changes in chromosome 11 in Wilms' tumours. Using a range of probes for regions 11p15, 11p13 and 11q we have screened DNA from 14 Wilms' tumours together with control DNA obtained from the patients' lymphocytes and their parents. We have been able to demonstrate loss of heterozygosity in 5 of the 14 different Wilms' tumours. In three of these five tumours, loss of heterozygosity did not involve markers for 11p13, 11p15.4 or the proximal region of 11p15.5, but only some markers assigned to the most distal part of 11p15.5. In two of these tumours we could demonstrate unequal mitotic recombination in 11p with breakpoints in the hypervariable regions 5' of the insulin gene and/or 3' of the HRASI proto-oncogene. In one tumour, from a Beckwith-Wiedemann patient, all markers for the region 11q13-pter became hemizygous; the region 11q13-qter remained heterozygous. These results demonstrate that loss of heterozygosity in Wilms' tumours may not necessarily involve the proposed Wilms' tumours locus at 11p13 but may be limited to 11p15.5. This suggests that not only the 11p13 region, but also the 11p15.5 region is involved in Wilms' tumour development. The possible role of both regions in the development of Wilms' tumour is discussed.
Mannens
M
M
Institute of Human Genetics, University of Amsterdam, The Netherlands.
Slater
R M
RM
Heyting
C
C
Bliek
J
J
de Kraker
J
J
Coad
N
N
de Pagter-Holthuizen
P
P
Pearson
P L
PL
D000483:Alleles; D015139:Blotting, Southern; D002648:Child; D002871:Chromosome Banding; D002880:Chromosomes, Human, Pair 11; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D015183:Restriction Mapping; D009396:Wilms Tumor / Q000235:genetics*
D005819:Genetic Markers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas