Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
Pignata, Laura (Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso')
Palumbo, Orazio (Fondazione IRCCS Casa Sollievo della Sofferenza)
Cerrato, Flavia (University of Campania 'Luigi Vanvitelli')
Acurzio, Basilia (Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso')
De Álava, Enrique (Universidad de Sevilla)
Roma, Josep (Hospital Universitari Vall d'Hebron)
Gallego, Soledad (Hospital Universitari Vall d'Hebron)
Català-Mora, Jaume 1973- (Hospital Sant Joan de Déu (Manresa))
Carella, Massimo (Fondazione IRCCS Casa Sollievo della Sofferenza)
Riccio, Andrea (Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso')
Verde, Gaetano (Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso')
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	About 7% of all children's malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presence of similar alterations in pediatric malignancies. Our results demonstrated that 35% of WT cases were affected by methylation abnormalities of multiple imprinted loci. However, differently from adult cancers, they were associated with either chromosome aberrations or normal chromosome profiles. Epigenotype-phenotype correlations indicated that these epimutations were more frequent in highly aggressive tumors, suggesting the use of multiple methylation imprinting defects as a new informative marker for WT. The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children's malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15. 5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is different.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Nephroblastoma ; Genomic imprinting ; DNA methylation ; Chromosome aberrations
Publicado en:	Cancers, Vol. 12 (november 2020) , ISSN 2072-6694

DOI: 10.3390/cancers12113411
PMID: 33217932

13 p, 2.2 MB

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