MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours.
MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours.
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在原发性和复发性叶绿体肿瘤中，MED12，TERT启动子和RBM15突变。
DOI：
10.1038/bjc.2017.450
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发表时间：
2018-01
影响因子：
8.8
通讯作者：
Sawyer EJ
中科院分区：
文献类型：
--
作者：
Garcia-Dios DA;Levi D;Shah V;Gillett C;Simpson MA;Hanby A;Tomlinson I;Sawyer EJ
MED12 和 TERT 启动子突变已被证明是叶状肿瘤 (PT) 中最常见的体细胞突变。本研究的目的是确定复发性 PT 中这些突变的频率，评估 TERT 启动子突变是否有助于区分纤维腺瘤 (FA) 和 PT，并识别可能驱动恶性进展的新突变。对 75 例原发 PT、21 例复发、19 例单 FA 和 2 例良性 PT 多发 FA 病例中的 MED12 和 TERT 启动子进行了 Sanger 测序。对一个临界 PT 进行全外显子组测序。复发性 PT 和多个 FA 在 MED12 中显示时间不一致，但在 TERT 中则不然。复发样本确实获得了 TERT 突变，而复发良性 PT 更有可能在两个基因中都发生突变。在多个 FA/PT 的情况下，TERT 突变无助于区分良性 PT 和 FA。外显子组测序揭示了 RBM15 中的无义突变，桑格测序揭示了恶性/边缘性 PT 中的另外三个 RBM15 突变。这项研究表明，与 TERT 突变不同，MED12 突变在同步和复发 PT 中可能是异质的。我们还表明，RBM15 突变可能在交界性/恶性 PT 的发病机制中发挥重要作用。
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. 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. 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. 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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