MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast

Histopathology. 2015 Nov;67(5):719-29. doi: 10.1111/his.12712. Epub 2015 May 24.


Aims: Somatic mutations in exon 2 of the mediator complex subunit 12 (MED12) gene have been identified in 60% of breast fibroadenomas (FAs). The aim of this study was to define whether phyllodes tumours (PTs) would harbour MED12 somatic mutations in a way akin to FAs.

Methods and results: A collection of 73 fibroepithelial tumours (including 26 FAs, 25 benign PTs, nine borderline PTs and 13 malignant PTs) from 64 patients was retrieved from the authors' institution. Sections from formalin-fixed paraffin-embedded (FFPE) blocks were microdissected to ensure an enrichment in neoplastic stromal elements of >70%. DNA samples extracted from tumour and matched normal tissues were subjected to Sanger sequencing of exon 2 of the MED12 gene. MED12 exon 2 somatic mutations, including 28 somatic single nucleotide variants and 19 insertions and deletions, were found in 65%, 88%, 78% and 8% of FAs, benign PTs, borderline PTs and malignant PTs, respectively. Malignant PTs harboured MED12 exon 2 somatic mutations significantly less frequently than FAs, benign and borderline PTs.

Conclusions: Although MED12 exon 2 somatic mutations probably constitute the driver genetic event of most FAs, benign and borderline PTs, our results suggest that the majority of malignant PTs may be driven by other genetic/epigenetic alterations.

Keywords: MED12; breast; fibroepithelial tumours; sequencing; somatic mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Female
  • Fibroadenoma / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mediator Complex / genetics*
  • Microdissection
  • Mutation
  • Phyllodes Tumor / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • MED12 protein, human
  • Mediator Complex