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Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma

Pineoblastoma is a rare and highly aggressive brain cancer of childhood, histologically belonging to the spectrum of primitive neuroectodermal tumors. Patients with germline mutations in DICER1, a ribonuclease involved in microRNA processing, have increased risk of pineoblastoma, but genetic drivers...

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Autores principales: Snuderl, Matija, Kannan, Kasthuri, Pfaff, Elke, Wang, Shiyang, Stafford, James M., Serrano, Jonathan, Heguy, Adriana, Ray, Karina, Faustin, Arline, Aminova, Olga, Dolgalev, Igor, Stapleton, Stacie L., Zagzag, David, Chiriboga, Luis, Gardner, Sharon L., Wisoff, Jeffrey H., Golfinos, John G., Capper, David, Hovestadt, Volker, Rosenblum, Marc K., Placantonakis, Dimitris G., LeBoeuf, Sarah E., Papagiannakopoulos, Thales Y., Chavez, Lukas, Ahsan, Sama, Eberhart, Charles G., Pfister, Stefan M., Jones, David T. W., Karajannis, Matthias A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054684/
https://www.ncbi.nlm.nih.gov/pubmed/30030436
http://dx.doi.org/10.1038/s41467-018-05029-3
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author Snuderl, Matija
Kannan, Kasthuri
Pfaff, Elke
Wang, Shiyang
Stafford, James M.
Serrano, Jonathan
Heguy, Adriana
Ray, Karina
Faustin, Arline
Aminova, Olga
Dolgalev, Igor
Stapleton, Stacie L.
Zagzag, David
Chiriboga, Luis
Gardner, Sharon L.
Wisoff, Jeffrey H.
Golfinos, John G.
Capper, David
Hovestadt, Volker
Rosenblum, Marc K.
Placantonakis, Dimitris G.
LeBoeuf, Sarah E.
Papagiannakopoulos, Thales Y.
Chavez, Lukas
Ahsan, Sama
Eberhart, Charles G.
Pfister, Stefan M.
Jones, David T. W.
Karajannis, Matthias A.
author_facet Snuderl, Matija
Kannan, Kasthuri
Pfaff, Elke
Wang, Shiyang
Stafford, James M.
Serrano, Jonathan
Heguy, Adriana
Ray, Karina
Faustin, Arline
Aminova, Olga
Dolgalev, Igor
Stapleton, Stacie L.
Zagzag, David
Chiriboga, Luis
Gardner, Sharon L.
Wisoff, Jeffrey H.
Golfinos, John G.
Capper, David
Hovestadt, Volker
Rosenblum, Marc K.
Placantonakis, Dimitris G.
LeBoeuf, Sarah E.
Papagiannakopoulos, Thales Y.
Chavez, Lukas
Ahsan, Sama
Eberhart, Charles G.
Pfister, Stefan M.
Jones, David T. W.
Karajannis, Matthias A.
author_sort Snuderl, Matija
collection PubMed
description Pineoblastoma is a rare and highly aggressive brain cancer of childhood, histologically belonging to the spectrum of primitive neuroectodermal tumors. Patients with germline mutations in DICER1, a ribonuclease involved in microRNA processing, have increased risk of pineoblastoma, but genetic drivers of sporadic pineoblastoma remain unknown. Here, we analyzed pediatric and adult pineoblastoma samples (n = 23) using a combination of genome-wide DNA methylation profiling and whole-exome sequencing or whole-genome sequencing. Pediatric and adult pineoblastomas showed distinct methylation profiles, the latter clustering with lower-grade pineal tumors and normal pineal gland. Recurrent variants were found in genes involved in PKA- and NF-κB signaling, as well as in chromatin remodeling genes. We identified recurrent homozygous deletions of DROSHA, acting upstream of DICER1 in microRNA processing, and a novel microduplication involving chromosomal region 1q21 containing PDE4DIP (myomegalin), comprising the ancient DUF1220 protein domain. Expresion of PDE4DIP and DUF1220 proteins was present exclusively in pineoblastoma with PDE4DIP gain.
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spelling pubmed-60546842018-07-26 Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma Snuderl, Matija Kannan, Kasthuri Pfaff, Elke Wang, Shiyang Stafford, James M. Serrano, Jonathan Heguy, Adriana Ray, Karina Faustin, Arline Aminova, Olga Dolgalev, Igor Stapleton, Stacie L. Zagzag, David Chiriboga, Luis Gardner, Sharon L. Wisoff, Jeffrey H. Golfinos, John G. Capper, David Hovestadt, Volker Rosenblum, Marc K. Placantonakis, Dimitris G. LeBoeuf, Sarah E. Papagiannakopoulos, Thales Y. Chavez, Lukas Ahsan, Sama Eberhart, Charles G. Pfister, Stefan M. Jones, David T. W. Karajannis, Matthias A. Nat Commun Article Pineoblastoma is a rare and highly aggressive brain cancer of childhood, histologically belonging to the spectrum of primitive neuroectodermal tumors. Patients with germline mutations in DICER1, a ribonuclease involved in microRNA processing, have increased risk of pineoblastoma, but genetic drivers of sporadic pineoblastoma remain unknown. Here, we analyzed pediatric and adult pineoblastoma samples (n = 23) using a combination of genome-wide DNA methylation profiling and whole-exome sequencing or whole-genome sequencing. Pediatric and adult pineoblastomas showed distinct methylation profiles, the latter clustering with lower-grade pineal tumors and normal pineal gland. Recurrent variants were found in genes involved in PKA- and NF-κB signaling, as well as in chromatin remodeling genes. We identified recurrent homozygous deletions of DROSHA, acting upstream of DICER1 in microRNA processing, and a novel microduplication involving chromosomal region 1q21 containing PDE4DIP (myomegalin), comprising the ancient DUF1220 protein domain. Expresion of PDE4DIP and DUF1220 proteins was present exclusively in pineoblastoma with PDE4DIP gain. Nature Publishing Group UK 2018-07-20 /pmc/articles/PMC6054684/ /pubmed/30030436 http://dx.doi.org/10.1038/s41467-018-05029-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Snuderl, Matija
Kannan, Kasthuri
Pfaff, Elke
Wang, Shiyang
Stafford, James M.
Serrano, Jonathan
Heguy, Adriana
Ray, Karina
Faustin, Arline
Aminova, Olga
Dolgalev, Igor
Stapleton, Stacie L.
Zagzag, David
Chiriboga, Luis
Gardner, Sharon L.
Wisoff, Jeffrey H.
Golfinos, John G.
Capper, David
Hovestadt, Volker
Rosenblum, Marc K.
Placantonakis, Dimitris G.
LeBoeuf, Sarah E.
Papagiannakopoulos, Thales Y.
Chavez, Lukas
Ahsan, Sama
Eberhart, Charles G.
Pfister, Stefan M.
Jones, David T. W.
Karajannis, Matthias A.
Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
title Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
title_full Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
title_fullStr Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
title_full_unstemmed Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
title_short Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma
title_sort recurrent homozygous deletion of drosha and microduplication of pde4dip in pineoblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054684/
https://www.ncbi.nlm.nih.gov/pubmed/30030436
http://dx.doi.org/10.1038/s41467-018-05029-3
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