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BackgroundMED12 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.MethodsMED12 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.ResultsRecurrent 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.ConclusionsThis 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.

Original publication

DOI

10.1038/bjc.2017.450

Type

Journal article

Journal

British journal of cancer

Publication Date

01/2018

Volume

118

Pages

277 - 284

Addresses

School of Cancer and Pharmaceutical Sciences, Guy's Hospital, King's College London, London SE1 9RT, UK.

Keywords

Humans, Phyllodes Tumor, Breast Neoplasms, Neoplasm Recurrence, Local, Telomerase, RNA-Binding Proteins, Base Sequence, Mutation, Adult, Female, Promoter Regions, Genetic, Young Adult, Mediator Complex