TY - JOUR
T1 - Both epimutations and chromosome aberrations affect multiple imprinted loci in aggressive wilms tumors
AU - Pignata, Laura
AU - Palumbo, Orazio
AU - Cerrato, Flavia
AU - Acurzio, Basilia
AU - de Álava, Enrique
AU - Roma, Josep
AU - Gallego, Soledad
AU - Mora, Jaume
AU - Carella, Massimo
AU - Riccio, Andrea
AU - Verde, Gaetano
N1 - Funding Information:
Funding: This study was funded by the Ministry of Education, Universities and Research, Research Projects of National Interest (MIUR PRIN) 2015 grant no JHLY35, Telethon-Italia grant no GGP1513, AIRC grant no. IG18671 (A.R.).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Chromosome aberrations
KW - DNA methylation
KW - Genomic imprinting
KW - Nephroblastoma
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U2 - 10.3390/cancers12113411
DO - 10.3390/cancers12113411
M3 - Article
AN - SCOPUS:85096166919
VL - 12
SP - 1
EP - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 11
M1 - 3411
ER -