Activation of the Wnt/ß-catenin pathway is common in wilms tumor, but rarely through ß-catenin mutation and APC promoter methylation.
Pediatr Surg Int
; 32(12): 1141-1146, 2016 Dec.
Article
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| MEDLINE
| ID: mdl-27679509
ABSTRACT
PURPOSE:
The Wnt/ß-catenin pathway is known to be crucial for the regulation of embryogenesis and cell differentiation, and its constitutive activation is associated with a wide range of malignancies. There are two major principles for an activated Wnt/ß-catenin pathway. The first is caused by the failure of the destruction complex, mainly due to the decreased expression of the tumor suppressor gene adenomatous polyposis coli (APC); the second is the mutation of the ß-catenin (CTNNB1) protein itself. Wilms tumors (WTs) are also thought to be malignancies with a high rate of Wnt/ß-catenin pathway activation. The aim of this study was to analyze a large cohort of WT for activated Wnt/ß-catenin pathway.METHODS:
The transcription of axis inhibition protein 2 (AXIN2) and APC was analyzed by real-time PCR. Expression was compared with those in healthy renal tissues as a control. Methylation status of the APC promoter was measured by pyrosequencing and correlated with APC expression. Finally, the mutations of CTNNB1 itself were detected by Sanger sequencing.RESULTS:
The analysis was done in a cohort of 103 WTs, treated in our institution. There was a significant overexpression of AXIN2 in WTs (P < 0.0001), with 33 (32 %) tumors showing higher expression (median + 3× SD) than normal kidney tissue. In contrast, the expression of APC as well as its promoter methylation did not differ from control (P = 0.78; P = 0.82). Finally, there were only seven (6.8 %) mutations detectable in CTNNB1, and five out of seven were seen in WTs with AXIN2 overexpression.CONCLUSION:
The finding that AXIN2, one of the major Wnt target genes, is overexpressed in our cohort of WTs, is indicative for the activation of the Wnt/ß-catenin pathway. However, neither the alteration of APC nor frequent CTNNB1 mutations were seen in our analyses. Therefore, other mechanisms might be responsible for the common activation of the Wnt/ß-catenin pathway.Palabras clave
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regiones Promotoras Genéticas
/
Tumor de Wilms
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Metilación de ADN
/
Proteínas Wnt
/
Beta Catenina
/
Mutación
Límite:
Adolescent
/
Child
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Child, preschool
/
Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatr Surg Int
Asunto de la revista:
PEDIATRIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania