title: MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases.
abstract: OBJECTIVE
  To determine the frequency of MED12 mutations in a series of 112 breast phyllodes tumours, and to correlate the findings with clinicopathological parameters and survival outcomes.
  
  
  METHODS
  Phyllodes tumours from the Department of Pathology, Singapore General Hospital, were classified into benign, borderline and malignant categories. Genomic DNA from formalin-fixed paraffin-embedded phyllodes tumours was extracted, purified and subjected to ultra-deep-targeted amplicon sequencing across exon 2 of the MED12 gene. Sequencing was performed on the Illumina MiSeq next-generation sequencing platform and bioinformatics analysis applied. Appropriate statistical analyses were carried out.
  
  
  RESULTS
  There were 66 benign, 32 borderline and 14 malignant tumours, with 43 (65.1%), 21 (65.6%) and 6 (42.8%) disclosing MED12 mutations (missense, splice site, indel), respectively. For 97 cases with available follow-up, there were 10 (10.3%) recurrences. Patients with phyllodes tumours that harboured MED12 mutations experienced improved disease-free survivals, with higher recurrence likelihood in those without MED12 mutations (HR 9.99, 95% CIs 1.55 to 64.42, p=0.015).
  
  
  CONCLUSIONS
  Similar to fibroadenomas, phyllodes tumours show a high frequency of MED12 mutations, affirming the close biological relationship between these fibroepithelial neoplasms.
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Cedric Chuan Young
authors.initials: CC
authors.lastname: Ng
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Weng Khong
authors.initials: WK
authors.lastname: Lim
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Vikneswari
authors.initials: V
authors.lastname: Rajasegaran
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Nur Diyana Md
authors.initials: ND
authors.lastname: Nasir
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Jeffrey Chun Tatt
authors.initials: JC
authors.lastname: Lim
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Syed Ahmed
authors.initials: SA
authors.lastname: Salahuddin
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Jabed
authors.initials: J
authors.lastname: Iqbal
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Inny
authors.initials: I
authors.lastname: Busmanis
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Angela Phek Yoon
authors.initials: AP
authors.lastname: Chong
authors.affiliation: Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D056892:Mediator Complex / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D003557:Phyllodes Tumor / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; C460107:MED12 protein, human; D056892:Mediator Complex
keywords: BREAST; CELL BIOLOGY; GENETICS