Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Guertl, B; Ratschek, M; Harms, D; Jaenig, U; Leuschner, I; Poremba, C; Hoefler, G.
Clonality and loss of heterozygosity of WT genes are early events in the pathogenesis of nephroblastomas.
Hum Pathol. 2003; 34(3):278-281
Doi: 10.1053/hupa.2003.32
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Gürtl-Lackner Barbara
- Höfler Gerald
- Co-Autor*innen der Med Uni Graz
- Ratschek Manfred
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- Abstract:
- Nephrogenic rests (NRs), putative precursor lesions of nephroblastomas (Wilms' tumors), are found in 25% to 40% of kidneys presenting with nephroblastomas. Nephroblastomas are clonal tumors that, according to a genetic multistep model, are thought to arise as subclonal proliferations from NRs by accumulating genetic alterations. Different candidate genes for the pathogenesis of nephroblastomas have been identified, including those at chromosomes 11p13 (WT1 gene), 11p15 (WT2 gene), and 16q (WT3 gene). We investigated clonality and loss of heterozygosity (LOH) at these loci in different subtypes of NR. After microdissection under microscopic control, we analyzed a highly polymorphic locus of the human androgen receptor gene (HUMARA) for nonrandom X-inactivation of genomic DNA using a methylation-sensitive restriction enzyme to investigate clonality. Out of 14 patients, we found that 1 case each of adenomatous and hyperplastic NR and 2 of 7 cases of sclerosing NR were monoclonal. Five patients were noninformative. We assessed LOH at chromosomes 11p13, 11p15, and 16q by analyzing polymorphic gene loci at these regions. One hyperplastic NR and the corresponding tumor showed LOH at 11p13 and 11p15; 1 sclerosing NR and the corresponding tumor exhibited LOH at chromosome 16q. We demonstrate for the first time that sclerosing NRs can exhibit genetic alterations found in nephroblastomas, namely monoclonality and LOH at the WT gene loci. The histological morphology is no different between NRs with these genetic alterations and NRs without them. We conclude that these genetic changes are early events in the multistep genetic pathogenesis of nephroblastomas; however, they do not seem to fully determine a malignant potential of NR.
- Find related publications in this database (using NLM MeSH Indexing)
- Child, Preschool -
- Chromosomes -
- Chromosomes, Human, Pair 16 -
- Clone Cells -
- Female -
- Genes, Wilms Tumor -
- Humans -
- Hyperplasia -
- Infant -
- Kidney Neoplasms - genetics Kidney Neoplasms - pathology
- Loss of Heterozygosity -
- Precancerous Conditions - genetics Precancerous Conditions - pathology
- Receptors, Androgen - genetics
- Sclerosis -
- Wilms Tumor - genetics Wilms Tumor - pathology
- Find related publications in this database (Keywords)
- nephrogenic rest
- clonality
- human androgen receptor gene
- loss of heterozygosity
- Wilms' tumor gene