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MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours

BACKGROUND: MED12 and TERT promoter mutations have been shown to be the most common somatic mutations in phyllodes tumours (PTs). The aims of this study were to determine the frequency of these mutations in recurrent PTs, assess whether TERT promoter mutations could be helpful in distinguishing fibr...

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Autores principales: Garcia-Dios, Diego A, Levi, Dina, Shah, Vandna, Gillett, Cheryl, Simpson, Michael A, Hanby, Andrew, Tomlinson, Ian, Sawyer, Elinor J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785756/
https://www.ncbi.nlm.nih.gov/pubmed/29315289
http://dx.doi.org/10.1038/bjc.2017.450
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author Garcia-Dios, Diego A
Levi, Dina
Shah, Vandna
Gillett, Cheryl
Simpson, Michael A
Hanby, Andrew
Tomlinson, Ian
Sawyer, Elinor J
author_facet Garcia-Dios, Diego A
Levi, Dina
Shah, Vandna
Gillett, Cheryl
Simpson, Michael A
Hanby, Andrew
Tomlinson, Ian
Sawyer, Elinor J
author_sort Garcia-Dios, Diego A
collection PubMed
description BACKGROUND: MED12 and TERT promoter mutations have been shown to be the most common somatic mutations in phyllodes tumours (PTs). The aims of this study were to determine the frequency of these mutations in recurrent PTs, assess whether TERT promoter mutations could be helpful in distinguishing fibroadenomas (FAs) from PTs and identify novel mutations that may be driving malignant progression. METHODS: MED12 and the TERT promoter were Sanger sequenced in 75 primary PTs, 21 recurrences, 19 single FAs and 2 cases of multiple FAs with benign PTs. Whole-exome sequencing was performed on one borderline PT. RESULTS: Recurrent PTs and multiple FAs showed temporal discordance in MED12 but not TERT. Recurrent samples did acquire TERT mutations, with recurrent benign PTs more likely to have mutations in both genes. TERT mutations were not helpful in differentiating between benign PTs and FAs in cases of multiple FAs/PTs. Exome sequencing revealed a nonsense mutation in RBM15 and Sanger sequencing revealed another three RBM15 mutations in malignant/borderline PTs. CONCLUSIONS: This study has shown that MED12 mutations can be heterogeneous in both synchronous and recurrent PTs unlike TERT mutations. We have also shown that RBM15 mutations may be important in the pathogenesis of borderline/malignant PTs.
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spelling pubmed-57857562019-01-01 MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours Garcia-Dios, Diego A Levi, Dina Shah, Vandna Gillett, Cheryl Simpson, Michael A Hanby, Andrew Tomlinson, Ian Sawyer, Elinor J Br J Cancer Genetics & Genomics BACKGROUND: MED12 and TERT promoter mutations have been shown to be the most common somatic mutations in phyllodes tumours (PTs). The aims of this study were to determine the frequency of these mutations in recurrent PTs, assess whether TERT promoter mutations could be helpful in distinguishing fibroadenomas (FAs) from PTs and identify novel mutations that may be driving malignant progression. METHODS: MED12 and the TERT promoter were Sanger sequenced in 75 primary PTs, 21 recurrences, 19 single FAs and 2 cases of multiple FAs with benign PTs. Whole-exome sequencing was performed on one borderline PT. RESULTS: Recurrent PTs and multiple FAs showed temporal discordance in MED12 but not TERT. Recurrent samples did acquire TERT mutations, with recurrent benign PTs more likely to have mutations in both genes. TERT mutations were not helpful in differentiating between benign PTs and FAs in cases of multiple FAs/PTs. Exome sequencing revealed a nonsense mutation in RBM15 and Sanger sequencing revealed another three RBM15 mutations in malignant/borderline PTs. CONCLUSIONS: This study has shown that MED12 mutations can be heterogeneous in both synchronous and recurrent PTs unlike TERT mutations. We have also shown that RBM15 mutations may be important in the pathogenesis of borderline/malignant PTs. Nature Publishing Group 2018-01 2018-01-09 /pmc/articles/PMC5785756/ /pubmed/29315289 http://dx.doi.org/10.1038/bjc.2017.450 Text en Copyright © 2018 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Genetics & Genomics
Garcia-Dios, Diego A
Levi, Dina
Shah, Vandna
Gillett, Cheryl
Simpson, Michael A
Hanby, Andrew
Tomlinson, Ian
Sawyer, Elinor J
MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours
title MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours
title_full MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours
title_fullStr MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours
title_full_unstemmed MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours
title_short MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours
title_sort med12, tert promoter and rbm15 mutations in primary and recurrent phyllodes tumours
topic Genetics & Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785756/
https://www.ncbi.nlm.nih.gov/pubmed/29315289
http://dx.doi.org/10.1038/bjc.2017.450
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