MED12 exon 2 mutations in phyllodes tumors of the breast.
MED12 exon 2 mutations in phyllodes tumors of the breast.
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DOI：
10.1002/cam4.462
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发表时间：
2015-07
期刊：
影响因子：
4
通讯作者：
Ohta T
中科院分区：
文献类型：
--
作者：
Nagasawa S;Maeda I;Fukuda T;Wu W;Hayami R;Kojima Y;Tsugawa K;Ohta T
MED12 的外显子 2（转录介质复合物的一个亚基）在子宫肌瘤和乳腺纤维腺瘤中经常发生突变；然而，它在其他肿瘤中很少发生突变。尽管在子宫平滑肌肉瘤中也发现了突变，但频率明显低于子宫平滑肌瘤。在这里，我们检查了叶状肿瘤中的 MED12 突变，叶状肿瘤是另一种双相肿瘤，具有与乳腺纤维腺瘤相关的上皮和间质成分。通过 Sanger 测序分析了 9 个纤维腺瘤和 11 个叶状肿瘤中 MED12 外显子 2 的突变。还使用 Ion Torrent 新一代测序分析了一组癌症和肉瘤相关基因。观察到纤维腺瘤中的 6 种突变，包括之前报道的突变（6/9，67%），以及叶状肿瘤中的 5 种突变（5/11，45%）。叶状肿瘤中的三个突变是 Gly44 的错义突变，这种突变在子宫平滑肌瘤和乳腺纤维腺瘤中很常见。此外，在叶状肿瘤中观察到两个缺失突变（框内 c.133_144del12 和剪接受体 c.100-68_137del106 丢失）。下一代测序未观察到其他复发突变。叶状肿瘤中 MED12 外显子 2 的频繁突变表明，其可能与子宫平滑肌瘤（子宫平滑肌肉瘤和乳腺纤维腺瘤的一个亚组）具有相同的遗传病因。
Exon 2 of MED12, a subunit of the transcriptional mediator complex, has been frequently mutated in uterine leiomyomas and breast fibroadenomas; however, it has been rarely mutated in other tumors. Although the mutations were also found in uterine leiomyosarcomas, the frequency was significantly lower than in uterine leiomyomas. Here, we examined the MED12 mutation in phyllodes tumors, another biphasic tumor with epithelial and stromal components related to breast fibroadenomas. Mutations in MED12 exon 2 were analyzed in nine fibroadenomas and eleven phyllodes tumors via Sanger sequencing. A panel of cancer- and sarcoma-related genes was also analyzed using Ion Torrent next-generation sequencing. Six mutations in fibroadenomas, including those previously reported (6/9, 67%), and five mutations in phyllodes tumors (5/11, 45%) were observed. Three mutations in the phyllodes tumors were missense mutations at Gly44, which is common in uterine leiomyomas and breast fibroadenomas. In addition, two deletion mutations (in-frame c.133_144del12 and loss of splice acceptor c.100-68_137del106) were observed in the phyllodes tumors. No other recurrent mutation was observed with next-generation sequencing. Frequent mutations in MED12 exon 2 in the phyllodes tumors suggest that it may share genetic etiology with uterine leiomyoma, a subgroup of uterine leiomyosarcomas and breast fibroadenoma.