IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-04950-x.html
   My bibliography  Save this article

KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary

Author

Listed:
  • R. Tyler Hillman

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Joseph Celestino

    (The University of Texas MD Anderson Cancer Center)

  • Christopher Terranova

    (The University of Texas MD Anderson Cancer Center)

  • Hannah C. Beird

    (The University of Texas MD Anderson Cancer Center)

  • Curtis Gumbs

    (The University of Texas MD Anderson Cancer Center)

  • Latasha Little

    (The University of Texas MD Anderson Cancer Center)

  • Tri Nguyen

    (The University of Texas MD Anderson Cancer Center)

  • Rebecca Thornton

    (The University of Texas MD Anderson Cancer Center)

  • Samantha Tippen

    (The University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Karen H. Lu

    (The University of Texas MD Anderson Cancer Center)

  • David M. Gershenson

    (The University of Texas MD Anderson Cancer Center)

  • Kunal Rai

    (The University of Texas MD Anderson Cancer Center)

  • Russell R. Broaddus

    (The University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

Abstract

Adult-type granulosa cell tumors of the ovary (aGCTs) are rare gynecologic malignancies that exhibit a high frequency of somatic FOXL2 c.C402G (p.Cys134Trp) mutation. Treatment of relapsed aGCT remains a significant clinical challenge. Here we show, using whole-exome and cancer gene panel sequencing of 79 aGCTs from two independent cohorts, that truncating mutation of the histone lysine methyltransferase gene KMT2D (also known as MLL2) is a recurrent somatic event in aGCT. Mono-allelic KMT2D-truncating mutations are more frequent in recurrent (10/44, 23%) compared with primary (1/35, 3%) aGCTs (p = 0.02, two-sided Fisher’s exact test). IHC detects additional non-KMT2D-mutated aGCTs with loss of nuclear KMT2D expression, suggesting that non-genetic KMT2D inactivation may occur in this tumor type. These findings identify KMT2D inactivation as a novel driver event in aGCTs and suggest that mutation of this gene may increase the risk of disease recurrence.

Suggested Citation

  • R. Tyler Hillman & Joseph Celestino & Christopher Terranova & Hannah C. Beird & Curtis Gumbs & Latasha Little & Tri Nguyen & Rebecca Thornton & Samantha Tippen & Jianhua Zhang & Karen H. Lu & David M., 2018. "KMT2D/MLL2 inactivation is associated with recurrence in adult-type granulosa cell tumors of the ovary," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04950-x
    DOI: 10.1038/s41467-018-04950-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-04950-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-04950-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04950-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.