title: Mutational analysis of MED12 in fibroadenomas and phyllodes tumors of the breast by means of targeted next-generation sequencing.
abstract: We aimed to analyze MED12 mutation in fibroadenomas (FAs) and phyllodes tumors (PTs) of the breast, which are closely related and consist of epithelial and stromal components. Targeted deep-sequencing using next-generation sequencing was performed in FAs (n = 58) and PTs (n = 27). The frequency of MED12 mutant tumors was significantly higher (P = 0.016) in PTs (74.1 %) than in FAs. (46.6 %). As for FAs, this frequency was significantly higher (P = 0.001) for intracanalicular type (69.0 %) than for other histological subtypes such as pericanalicular, organoid, and mastopathic types (24.1 %). Laser microdissection study revealed that stromal cells, but not epithelial cells, harbored MED12 mutations in both FAs and PTs. MED12 mutation is implicated in the pathogenesis of both FAs and PTs. The similarly high frequency of MED12 mutation in intracanalicular type FAs suggests that they are most closely related to PTs. It is thus speculated that FAs with MED12 mutation are more likely to progress to PTs.
authors.affiliation: Department of Breast and Endocrine Surgery, Faculty of Medicine, Osaka University, Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita City, Osaka, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Mishima
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kagara
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tanei
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Naoi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimoda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.forename: Kenzo
authors.initials: K
authors.lastname: Shimazu
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D018226:Fibroadenoma / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D003557:Phyllodes Tumor / Q000235:genetics* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex