• A Corrigendum to this article was published on 26 June 2014

This article has been updated

Abstract

Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 69% (9/13) of SCCOHT cases in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Change history

  • 13 June 2014

    In the version of this article initially published, there were errors in the numbers of tumors reported in the text. The abstract reports SMARCA4 mutations in 75% (9/12) of tumors. The correct numbers are 69% (9/13) of tumors. The main text reports immunohistochemical analysis of 15 tumors, with 6 tumors overlapping with the 12 cases sequenced. These should have been reported as 17 tumors, 8 of which were overlapping. The errors do not affect any of the analyses or conclusions in the paper. In addition, a secondary affiliation for author Pilar Ramos was erroneously omitted and should read "School of Life Sciences, Arizona State University, Tempe, Arizona, USA." The errors have been corrected in the HTML and PDF versions of the article.

References

  1. 1.

    , & Am. J. Surg. Pathol. 18, 1102–1116 (1994).

  2. 2.

    , , , & Med. Pediatr. Oncol. 32, 304–307 (1999).

  3. 3.

    , & Med. Oncol. 28, 766–770 (2011).

  4. 4.

    , , & Arch. Gynecol. Obstet. 284, 1277–1282 (2011).

  5. 5.

    , , , & Int. J. Gynecol. Pathol. 23, 330–336 (2004).

  6. 6.

    et al. Orphanet J. Rare Dis. 8, 33 (2013).

  7. 7.

    et al. Pol. J. Pathol. 64, 238–246 (2013).

  8. 8.

    et al. Pediatr. Blood Cancer 53, 1334–1336 (2009).

  9. 9.

    et al. J. Pediatr. Surg. 47, 588–592 (2012).

  10. 10.

    , , , & Pediatr. Blood Cancer 56, 7–15 (2011).

  11. 11.

    et al. PLoS ONE 7, e31346 (2012).

  12. 12.

    et al. Mol. Cell. Biol. 34, 1136–1144 (2014).

  13. 13.

    et al. Cancer Res. 73, 5508–5518 (2013).

  14. 14.

    et al. Proc. Natl. Acad. Sci. USA 111, 3128–3133 (2014).

  15. 15.

    et al. Nat. Med. 4, 844–847 (1998).

Download references

Acknowledgements

We particularly thank the families and patients who joined this institutional review board (IRB)-approved study for their critical contributions. We also thank the faculty and staff at TGen from the Macromolecular Analysis & Processing Center (G. Hostetter and J. LoBello) and the Office of Research Compliance & Quality Management (L. Nordstrom, S. Althoff and S. Buchholtz); the Children's Oncology Group for their samples; and B. Vanderhyden (University of Ottawa and Ottawa Hospital Research Institute) for BIN-67 cells. This study was supported by grants from the Marsha Rivkin Center for Ovarian Cancer Research, the Anne Rita Monahan Foundation, the Ovarian Cancer Alliance of Arizona, the Small Cell Ovarian Cancer Foundation and philanthropic support to the TGen Foundation. Further support was provided to A.N.K. and D.G.H. by the Terry Fox Research Initiative New Frontiers Program in Cancer and to A.N.K. by the Molecular Oncologic Pathology Fellowship of the Canadian Institutes of Health Research.

Author information

Author notes

    • Pilar Ramos
    •  & Anthony N Karnezis

    These authors contributed equally to this work.

    • David G Huntsman
    •  & Jeffrey M Trent

    These authors jointly directed this work.

Affiliations

  1. Division of Integrated Cancer Genomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, USA.

    • Pilar Ramos
    • , David W Craig
    • , Aleksandar Sekulic
    • , Megan L Russell
    • , William P D Hendricks
    • , Jason J Corneveaux
    • , Michael T Barrett
    • , Jeffrey Kiefer
    • , Victoria L Zismann
    • , Troy A McEachron
    • , Bodour Salhia
    • , Heather E Cunliffe
    •  & Jeffrey M Trent
  2. School of Life Sciences, Arizona State University, Tempe, Arizona, USA.

    • Pilar Ramos
  3. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

    • Anthony N Karnezis
    • , Sohrab P Shah
    •  & David G Huntsman
  4. Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

    • Anthony N Karnezis
    • , Leah M Prentice
    •  & David G Huntsman
  5. Department of Dermatology, Mayo Clinic, Scottsdale, Arizona, USA.

    • Aleksandar Sekulic
  6. Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

    • Karey Shumansky
    • , Yidong Yang
    •  & Sohrab P Shah
  7. Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

    • Marco A Marra
  8. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

    • Jaime Prat
    •  & Emanuela D'Angelo
  9. Department of Pathology, University Health Network, Toronto, Ontario, Canada.

    • Blaise A Clarke
  10. Department of Pediatric Hematology-Oncology, Children's Hospital of Alabama, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    • Joseph G Pressey
  11. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Creighton University School of Medicine and St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.

    • John H Farley
  12. Evergreen Hematology and Oncology, Spokane, Washington, USA.

    • Stephen P Anthony
  13. Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.

    • Richard B S Roden
  14. Department of Pathology, University of Otago, Dunedin, New Zealand.

    • Heather E Cunliffe

Authors

  1. Search for Pilar Ramos in:

  2. Search for Anthony N Karnezis in:

  3. Search for David W Craig in:

  4. Search for Aleksandar Sekulic in:

  5. Search for Megan L Russell in:

  6. Search for William P D Hendricks in:

  7. Search for Jason J Corneveaux in:

  8. Search for Michael T Barrett in:

  9. Search for Karey Shumansky in:

  10. Search for Yidong Yang in:

  11. Search for Sohrab P Shah in:

  12. Search for Leah M Prentice in:

  13. Search for Marco A Marra in:

  14. Search for Jeffrey Kiefer in:

  15. Search for Victoria L Zismann in:

  16. Search for Troy A McEachron in:

  17. Search for Bodour Salhia in:

  18. Search for Jaime Prat in:

  19. Search for Emanuela D'Angelo in:

  20. Search for Blaise A Clarke in:

  21. Search for Joseph G Pressey in:

  22. Search for John H Farley in:

  23. Search for Stephen P Anthony in:

  24. Search for Richard B S Roden in:

  25. Search for Heather E Cunliffe in:

  26. Search for David G Huntsman in:

  27. Search for Jeffrey M Trent in:

Contributions

Study concept and design: P.R., A.N.K., H.E.C., J.M.T. and D.G.H. Acquisition of data: P.R., A.N.K., M.L.R., J.J.C., B.S. and H.E.C. Sample contribution: J.P., E.D., B.A.C., J.G.P., J.H.F., S.P.A. and R.B.S.R. Data analysis: P.R., A.N.K., A.S., W.P.D.H., M.T.B., J.K., V.L.Z., B.S., T.A.M., J.M.T. and D.G.H. Bioinformatics data analysis: D.W.C., M.L.R., J.J.C., K.S., Y.Y., S.P.S., L.M.P. and M.A.M. Drafting of the manuscript: P.R., A.N.K., A.S., W.P.D.H., J.M.T. and D.G.H.

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Note, Supplementary Figures 1–4 and Supplementary Tables 1 and 3

Excel files

  1. 1.

    Supplementary Table 2

    Summary of whole-genome and exome sequencing metrics.

  2. 2.

    Supplementary Table 4

    SMARCA4 immunohistochemical analysis in primary ovarian and adnexal epithelial, sex cord stromal and germ cell tumors.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.2928

Further reading