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Non-fusion mutations in endometrial stromal sarcomas: what is the potential impact on tumourigenesis through cell cycle dysregulation?
  1. Snehal B Patel1,2,3,
  2. Colin McCormack1,4,
  3. Jennelle C Hodge1,5,6
  1. 1 Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
  2. 2 Molecular Diagnostics Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  3. 3 Strata Oncology, Ann Arbor, MI, United States
  4. 4 Baylor Scott & White Medical Center-Temple, Temple, TX, United States
  5. 5 Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA
  6. 6 Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, United States
  1. Correspondence to Dr Jennelle C Hodge, Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN 46202, USA; jhodge1{at}


Targeted next-generation sequencing using the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2 identified two significant point mutations in endometrial stromal sarcomas (ESS). Case 1 is a uterine mass from a quadragenarian woman with a karyotype lacking any known ESS rearrangements but demonstrated to have a CTNNB1-activating mutation (c.133T>C, p.[Ser45Pro]). Analysis of a uterine mass from case 2, a sexagenarian woman, revealed biallelic CDKN2A-inactivating mutations (c.172C>T, p.[Arg58Ter] and a deletion). Break-apart studies to identify YWHAE, JAZF1 and PHF1 rearrangements were negative in both tumours. We propose a model in which these point mutations may affect cell proliferation, converging at Wnt signalling and G1-S checkpoint control, that independently or in concert with a rare gene fusion result in ESS tumour development or progression.

  • sarcomas
  • cancer genetics
  • gynaecological pathology
  • molecular genetics
  • cell cycle regulation

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  • Handling editor Mona El-Bahrawy.

  • Correction notice This article has been corrected since it appeared Online First. In the table, Karotype column, Grade 1 row has been reformatted.

  • Contributors SBP and JCH contributed to the conception and design of the study, data analysis and production of figures and manuscript text. CM contributed to data acquisition, production of figures and review of the 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.