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MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases
  1. Cedric Chuan Young Ng1,2,
  2. Jing Tan1,2,
  3. Choon Kiat Ong1,2,
  4. Weng Khong Lim1,2,
  5. Vikneswari Rajasegaran1,2,
  6. Nur Diyana Md Nasir3,
  7. Jeffrey Chun Tatt Lim3,
  8. Aye Aye Thike3,
  9. Syed Ahmed Salahuddin3,
  10. Jabed Iqbal3,
  11. Inny Busmanis3,
  12. Angela Phek Yoon Chong3,
  13. Bin Tean Teh1,2,
  14. Puay Hoon Tan3
  1. 1Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore
  2. 2Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore
  3. 3Department of Pathology, Singapore General Hospital, Singapore
  1. Correspondence to Dr Puay Hoon Tan, Department of Pathology, Singapore General Hospital, Academia, Diagnostics Tower Level 7, 20 College Road, Singapore 169856, Singapore; tan.puay.hoon{at}sgh.com.sg

Abstract

Aim 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.

  • BREAST
  • CELL BIOLOGY
  • GENETICS

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