MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast Journal Article


Authors: Piscuoglio, S.; Murray, M.; Fusco, N.; Marchiò, C.; Loo, F. L.; Martelotto, L. G.; Schultheis, A. M.; Akram, M.; Weigelt, B.; Brogi, E.; Reis-Filho, J. S.
Article Title: MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast
Abstract: 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. © 2015 John Wiley & Sons Ltd.
Keywords: adult; controlled study; human tissue; middle aged; unclassified drug; major clinical study; sequence analysis; somatic mutation; exon; breast; cystosarcoma phylloides; prevalence; genetic variability; tissue section; breast tumor; tumor protein; cancer tissue; point mutation; tumor gene; dna extraction; sequencing; breast fibroadenoma; somatic mutations; indel mutation; med12; human; female; priority journal; article; fibroepithelial tumours; mediator complex subunit 12; phyllode tumor of the breast
Journal Title: Histopathology
Volume: 67
Issue: 5
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2015-11-01
Start Page: 719
End Page: 729
Language: English
DOI: 10.1111/his.12712
PROVIDER: scopus
PUBMED: 25855048
PMCID: PMC4996373
DOI/URL:
Notes: Export Date: 2 November 2015 -- Source: Scopus
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MSK Authors
  1. Melissa P Murray
    123 Murray
  2. Edi Brogi
    515 Brogi
  3. Muzaffar M Akram
    92 Akram
  4. Florence Lai Loo
    5 Loo
  5. Britta Weigelt
    633 Weigelt
  6. Nicola Fusco
    30 Fusco
  7. Caterina   Marchio
    27 Marchio