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Grill, C; Sunitsch, S; Hatz, M; Hauser-Kronberger, C; Leuschner, I; Hoefler, G; Guertl, B.
Activation of beta-catenin is a late event in the pathogenesis of nephroblastomas and rarely correlated with genetic changes of the APC gene.
Pathology. 2011; 43(7):702-706
Doi: 10.1097/PAT.0b013e32834bf65c
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
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Gürtl-Lackner Barbara
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Sunitsch Sandra
- Co-authors Med Uni Graz
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Höfler Gerald
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Hofstadler Martina
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- Abstract:
- AIMS: Activation of â-catenin has been identified as a possible mechanism for the development of nephroblastomas. In our study we investigated whether this activation occurs already in precursor lesions of nephroblastomas, called nephrogenic rests (NRs). Inactivation of the adenomatous polyposis coli (APC) protein is an important regulatory mechanism of activating â-catenin. We clarified the role of APC by assessing loss of heterozygosity (LOH) and possible mutations within the genomic region. METHODS: Activation of â-catenin was examined by immunohistochemistry identifying nuclear translocation. Two polymorphic loci of the APC gene were investigated for LOH and sequence analysis was performed for the mutation cluster region of the APC gene on formalin fixed, paraffin embedded samples. RESULTS: Four of the 18 nephroblastomas available for immunohistochemistry exhibited nuclear staining of â-catenin, but none of the NRs. Analysis of LOH revealed 14 homozygous samples, 10 heterozygous tumours and six tumours exhibiting LOH of the APC gene. One blastema-type nephroblastoma showed nuclear localisation of â-catenin in conjunction with LOH of the APC gene. Analysis of 12 nephroblastomas revealed no sequence aberration. CONCLUSION: Our results indicate that nuclear activation of â-catenin is a late event in the tumorigenesis of nephroblastomas coinciding in some tumours with LOH of the APC gene.
- Find related publications in this database (using NLM MeSH Indexing)
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Genes, APC -
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Humans -
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Immunohistochemistry -
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Kidney Neoplasms - genetics
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Mutation -
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Precancerous Conditions - genetics
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Reverse Transcriptase Polymerase Chain Reaction -
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Wilms Tumor - genetics
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beta Catenin - metabolism
- Find related publications in this database (Keywords)
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beta-catenin
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APC
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immunohistochemistry
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LOH
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mutation analysis
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nephroblastoma
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nephrogenic rest