Title | MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG, Schultheis AM, Akram M, Weigelt B, Brogi E, Reis-Filho JS |
Journal | Histopathology |
Volume | 67 |
Issue | 5 |
Pagination | 719-29 |
Date Published | 2015 Nov |
ISSN | 1365-2559 |
Keywords | Breast Neoplasms, Female, Fibroadenoma, High-Throughput Nucleotide Sequencing, Humans, Mediator Complex, Microdissection, Mutation, Phyllodes Tumor, Reverse Transcriptase Polymerase Chain Reaction |
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. |
DOI | 10.1111/his.12712 |
Alternate Journal | Histopathology |
PubMed ID | 25855048 |
PubMed Central ID | PMC4996373 |
Grant List | P30 CA008748 / CA / NCI NIH HHS / United States |
Related Faculty:
Florence L. Loo, M.D.