title: MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Salvatore
authors: S
authors: Piscuoglio
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Melissa
authors: M
authors: Murray
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|School of Pathology, University of Milan, Milan, Italy.
authors: Nicola
authors: N
authors: Fusco
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Medical Sciences, University of Turin, Turin, Italy.
authors: Caterina
authors: C
authors: Marchiò
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Florence L
authors: FL
authors: Loo
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Luciano G
authors: http://orcid.org/0000-0002-9625-1183
authors: LG
authors: Martelotto
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Anne M
authors: AM
authors: Schultheis
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Muzaffar
authors: M
authors: Akram
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Britta
authors: B
authors: Weigelt
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Edi
authors: E
authors: Brogi
authors: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Jorge S
authors: JS
authors: Reis-Filho
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D018226:Fibroadenoma / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056892:Mediator Complex / Q000235:genetics*; D042282:Microdissection; D009154:Mutation; D003557:Phyllodes Tumor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex
keywords: MED12; breast; fibroepithelial tumours; sequencing; somatic mutations