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MED12, TERT and RARA in fibroepithelial tumours of the breast
  1. Huan Ying Chang1,2,
  2. Valerie Cui Yun Koh2,
  3. Nur Diyana Md Nasir2,
  4. Cedric Chuan Young Ng3,4,
  5. Peiyong Guan3,5,
  6. Aye Aye Thike2,
  7. Bin Tean Teh3,4,
  8. Puay Hoon Tan2,6
  1. 1 Duke-NUS Medical School, Singapore, Singapore
  2. 2 Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
  3. 3 Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore
  4. 4 Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore
  5. 5 PhD Programme in Quantitative Biology and Medicine, Duke-NUS Medical School, Singapore, Singapore
  6. 6 Division of Pathology, Singapore General Hospital, Singapore, Singapore
  1. Correspondence to Professor Puay Hoon Tan, Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore; tan.puay.hoon{at}singhealth.com.sg

Abstract

Fibroepithelial tumours are biphasic neoplasms of the breast comprising the common benign fibroadenomas and the less common phyllodes tumours (PTs), which have recurrent potential. PTs are classified into benign, borderline or malignant, based on five histopathological criteria, with malignant PTs having the highest metastatic capability. Accurate diagnosis can be challenging due to the subjective assessment of histopathological parameters. Fibroadenomas bear morphological similarities to benign PTs, while borderline and malignant PTs can sometimes be difficult to distinguish from other spindle cell tumours of the breast. From clonality studies to whole-genome sequencing, much research has been conducted to elucidate the molecular pathogenesis of fibroepithelial tumours, which, in turn, have allowed leveraging the findings for diagnostic applications, including grading of PTs. The most noteworthy discovery was of recurrent MED12 mutations in both fibroadenomas and PTs. Subsequent studies also uncovered relatively frequent genetic mutations in TERT promoter and RARA. A customised panel of 16 most frequently mutated genes in fibroepithelial tissues has been compiled previously and has contributed to resolving a few diagnostic dilemmas. This review will introduce the 16 genes and focus on the top three that are most frequently mutated in fibroepithelial tumours: MED12, TERT, and RARA.

  • breast pathology
  • breast
  • molecular genetics
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Footnotes

  • Handling editor Des Richardson.

  • Contributors HYC conducted the literature review and drafted the manuscript with VCYK. NDMN and AAT provided the histology images. CCYN and PG created the lollipop charts of MED12, TERT promoter and RARA mutations. PHT formulated the scope of the review. PHT, CCYN and BTT edited the manuscript. All authors reviewed and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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