Breast Cancer Research and Treatment

, Volume 152, Issue 2, pp 305–312 | Cite as

Mutational analysis of MED12 in fibroadenomas and phyllodes tumors of the breast by means of targeted next-generation sequencing

  • Chieko Mishima
  • Naofumi Kagara
  • Tomonori Tanei
  • Yasuto Naoi
  • Masafumi Shimoda
  • Atsushi Shimomura
  • Kenzo Shimazu
  • Seung Jin Kim
  • Shinzaburo Noguchi
Preclinical study


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.


MED12 Somatic mutation Next-generation sequencing Fibroepithelial tumor 





Phyllodes tumor



We are grateful to Dr. Junichiro Ikeda for his help in the pathological diagnosis.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study complied with the current laws of Japan.

Supplementary material

10549_2015_3469_MOESM1_ESM.tif (75 kb)
Supplementary material 1 (TIFF 75 kb). Primers for next-generation sequencing of MED12. Two sets of primers were designed to amplify genomic DNA (gDNA) and complementary DNA (cDNA). Letters in bold type: primer sequences
10549_2015_3469_MOESM2_ESM.tif (233 kb)
Supplementary material 2 (TIFF 233 kb). MED12 mutation status of thirteen synchronous multiple tumors from six patients (a), and seven metachronous multiple tumors from three patients (b). Filled circle, fibroadenoma; circle with vertical lines, phyllodes tumor. Period after the resection of primary tumor (*); period after the resection of secondary tumor (**)
10549_2015_3469_MOESM3_ESM.doc (30 kb)
Supplementary material 3 (DOC 30 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Chieko Mishima
    • 1
  • Naofumi Kagara
    • 1
  • Tomonori Tanei
    • 1
  • Yasuto Naoi
    • 1
  • Masafumi Shimoda
    • 1
  • Atsushi Shimomura
    • 1
  • Kenzo Shimazu
    • 1
  • Seung Jin Kim
    • 1
  • Shinzaburo Noguchi
    • 1
  1. 1.Department of Breast and Endocrine Surgery, Faculty of MedicineOsaka University, Graduate School of MedicineSuita CityJapan

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