title: MED12 exon 2 mutations in phyllodes tumors of the breast.
abstract: 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.
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.|Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Satoi
authors: S
authors: Nagasawa
authors: Department of Pathology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Ichiro
authors: I
authors: Maeda
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Takayo
authors: T
authors: Fukuda
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Wenwen
authors: W
authors: Wu
authors: Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Ryosuke
authors: R
authors: Hayami
authors: Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Yasuyuki
authors: Y
authors: Kojima
authors: Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Ko-Ichiro
authors: K
authors: Tsugawa
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Tomohiko
authors: T
authors: Ohta
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D003557:Phyllodes Tumor / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex
keywords: Breast; MED12; mutation; phyllodes