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Basic Sciences
Polymerase Epsilon Exonuclease Domain Mutations in Ovarian Endometrioid Carcinoma
  1. Lien N. Hoang, MD*,†,
  2. Melissa K. McConechy, PhD*,†,
  3. Martin Köbel, MD‡,§,
  4. Michael Anglesio, PhD*,†,
  5. Janine Senz, BSc*,†,
  6. Malden Maassen∥,
  7. Stefan Kommoss, MD∥,
  8. Bo Meng, PhD,#,
  9. Lynne Postovit, PhD**,
  10. Linda E. Kelemen, ScD††,‡‡,
  11. Annette Staebler, MD∥,
  12. Sara Brucker, MD∥,
  13. Bernhard Krämer, MD∥,
  14. Jessica N. McAlpine, MD§§,
  15. C. Blake Gilks, MD*,†,
  16. David G. Huntsman, MD*,†,§§ and
  17. Cheng-Han Lee, MD, PhD,#
  1. *Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital;
  2. †University of British Columbia, Vancouver;
  3. ‡Department of Pathology and Laboratory Medicine, Calgary Laboratory Services;
  4. §University of Calgary, Calgary, Canada;
  5. ∥Department of Gynecology and Obstetrics, Tübingen University, Tübingen, Germany;
  6. Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital;
  7. #University of Alberta;
  8. **Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada;
  9. ††Department of Public Health Sciences, Medical University of South Carolina;
  10. ‡‡Hollings Cancer Center, Charleston, SC; and
  11. §§Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, Canada.
  1. Address correspondence and reprint requests to Cheng-Han Lee, MD, PhD, Department of Laboratory Medicine and Pathology, University of Alberta and Royal Alexandra Hospital, Room DTC 5002-16, 10240 Kingsway, Edmonton, Alberta, Canada T5H 3V9. E-mail: chlee2{at}ualberta.ca.

Abstract

Objective Polymerase epsilon (POLE) is a DNA polymerase with a proofreading (exonuclease) domain, responsible for the recognition and excision of mispaired bases, thereby allowing high-fidelity DNA replication to occur. The Cancer Genome Atlas research network recently identified an ultramutated group of endometrial carcinomas, characterized by mutations in POLE, and exceptionally high substitution mutation rates. These POLE mutated endometrial tumors were almost exclusively of the endometrioid histotype. The prevalence and patterns of POLE mutated tumors in endometrioid carcinomas of the ovary, however, have not been studied in detail.

Materials and Methods In this study, we investigate the frequency of POLE exonuclease domain mutations in a series of 89 ovarian endometrioid carcinomas.

Results We found POLE mutations in 4 of 89 (4.5%) cases, occurring in 3 of 23 (13%) International Federation of Gynecology and Obstetrics (FIGO) grade 1, 1 of 43 (2%) FIGO grade 2, and 0 of 23 (0%) FIGO grade 3 tumors. All mutations were somatic missense point mutations, occurring at the commonly reported hotspots, P286R and V411L. All 3 POLE-mutated FIGO grade 1 tumors displayed prototypical histology, and the POLE-mutated FIGO grade 2 tumor displayed morphologic heterogeneity with focally high-grade features. All 4 patients with POLE-mutated tumors followed an uneventful clinical course with no disease recurrence; however, this finding was not statistically significant (P = 0.59).

Conclusions The low rate of POLE mutations in ovarian endometrioid carcinoma and their predominance within the low FIGO grade tumors are in contrast to the findings in the endometrium.

  • POLE
  • Polymerase epsilon
  • Ovarian carcinoma
  • Endometrioid carcinoma
  • TCGA

https://doi.org/10.1097/IGC.0000000000000492

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    Footnotes

    • Both authors contributed equally to this study: Lien N. Hoang and Melissa K. McConechy.

    • The authors declare no conflicts of interest.