Garcia-Dios, DA, Levi, D, Shah, V et al. (5 more authors) (2018) MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours. British Journal of Cancer, 118. pp. 277-284. ISSN 0007-0920
Abstract
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | (c) 2018 Cancer Research UK. This is an article published in the British Journal of Cancer. It is released under the terms of the Creative Commons Attribution- NonCommercial-Share Alike 4.0 (CC BY-NC-SA) Unported License. |
Keywords: | phyllodes tumour; fibroadenoma; RBM15; MED12; TERT; heterogeneity |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Dec 2017 11:42 |
Last Modified: | 09 Jan 2019 09:19 |
Status: | Published |
Publisher: | Cancer Research UK |
Identification Number: | 10.1038/bjc.2017.450 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:124789 |