MED12 exon 2 mutations in phyllodes tumors of the breast

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. Mutations in exon 2 of MED12, a subunit of the transcriptional mediator complex, has been a hallmark of uterine leiomyomas and breast fibroadenomas; however, its status in phyllodes tumors, related to fibroadenomas, remains to be clarified. Here, we reveal the frequent mutations of MED12 exon 2 in phyllodes tumors, including a novel deletion involving the splice acceptor. The results suggest that phyllodes tumors may share a genetic etiology with uterine leiomyoma and breast fibroadenoma.