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Germline mutations and somatic inactivation of TRIM28 in Wilms tumour

Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumo...

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Autores principales: Halliday, Benjamin J., Fukuzawa, Ryuji, Markie, David M., Grundy, Richard G., Ludgate, Jackie L., Black, Michael A., Skeen, Jane E., Weeks, Robert J., Catchpoole, Daniel R., Roberts, Aedan G. K., Reeve, Anthony E., Morison, Ian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005459/
https://www.ncbi.nlm.nih.gov/pubmed/29912901
http://dx.doi.org/10.1371/journal.pgen.1007399
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author Halliday, Benjamin J.
Fukuzawa, Ryuji
Markie, David M.
Grundy, Richard G.
Ludgate, Jackie L.
Black, Michael A.
Skeen, Jane E.
Weeks, Robert J.
Catchpoole, Daniel R.
Roberts, Aedan G. K.
Reeve, Anthony E.
Morison, Ian M.
author_facet Halliday, Benjamin J.
Fukuzawa, Ryuji
Markie, David M.
Grundy, Richard G.
Ludgate, Jackie L.
Black, Michael A.
Skeen, Jane E.
Weeks, Robert J.
Catchpoole, Daniel R.
Roberts, Aedan G. K.
Reeve, Anthony E.
Morison, Ian M.
author_sort Halliday, Benjamin J.
collection PubMed
description Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis.
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spelling pubmed-60054592018-06-25 Germline mutations and somatic inactivation of TRIM28 in Wilms tumour Halliday, Benjamin J. Fukuzawa, Ryuji Markie, David M. Grundy, Richard G. Ludgate, Jackie L. Black, Michael A. Skeen, Jane E. Weeks, Robert J. Catchpoole, Daniel R. Roberts, Aedan G. K. Reeve, Anthony E. Morison, Ian M. PLoS Genet Research Article Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis. Public Library of Science 2018-06-18 /pmc/articles/PMC6005459/ /pubmed/29912901 http://dx.doi.org/10.1371/journal.pgen.1007399 Text en © 2018 Halliday et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Halliday, Benjamin J.
Fukuzawa, Ryuji
Markie, David M.
Grundy, Richard G.
Ludgate, Jackie L.
Black, Michael A.
Skeen, Jane E.
Weeks, Robert J.
Catchpoole, Daniel R.
Roberts, Aedan G. K.
Reeve, Anthony E.
Morison, Ian M.
Germline mutations and somatic inactivation of TRIM28 in Wilms tumour
title Germline mutations and somatic inactivation of TRIM28 in Wilms tumour
title_full Germline mutations and somatic inactivation of TRIM28 in Wilms tumour
title_fullStr Germline mutations and somatic inactivation of TRIM28 in Wilms tumour
title_full_unstemmed Germline mutations and somatic inactivation of TRIM28 in Wilms tumour
title_short Germline mutations and somatic inactivation of TRIM28 in Wilms tumour
title_sort germline mutations and somatic inactivation of trim28 in wilms tumour
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005459/
https://www.ncbi.nlm.nih.gov/pubmed/29912901
http://dx.doi.org/10.1371/journal.pgen.1007399
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