Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
Por:
Pignata L, Palumbo O, Cerrato F, Acurzio B, de Álava E, Roma J, Gallego S, Mora J, Carella M, Riccio A and Verde G
Publicada:
1 nov 2020
Ahead of Print:
18 nov 2020
Resumen:
Simple Summary
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.
Filiaciones:
Pignata L:
Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' CNR, 80131-Napoli, Italy
Palumbo O:
Division of Medical Genetics, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo (FG), Italy
Cerrato F:
Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy
Acurzio B:
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' CNR, 80131-Napoli, Italy
de Álava E:
Department of Pathology, Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, 41013 Seville, Spain
Department of Normal and Pathological Cytology and Histology, School of Medicine, University of Seville, 08035 Seville, Spain
Roma J:
Group of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute-Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
Gallego S:
Group of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute-Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
Mora J:
Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
Carella M:
Division of Medical Genetics, Fondazione IRCCS "Casa Sollievo della Sofferenza", 71013 San Giovanni Rotondo (FG), Italy
Riccio A:
Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' CNR, 80131-Napoli, Italy
Verde G:
Department of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', 81100 Caserta, Italy
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' CNR, 80131-Napoli, Italy
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