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High grade serous ovarian carcinomas originate in the fallopian tube

Author

Listed:
  • S. Intidhar Labidi-Galy

    (Dana-Farber Cancer Institute and Harvard Medical School
    Geneva University Hospitals)

  • Eniko Papp

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Personal Genome Diagnostics)

  • Dorothy Hallberg

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Noushin Niknafs

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Institute for Computational Medicine, Johns Hopkins University)

  • Vilmos Adleff

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Michael Noe

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Rohit Bhattacharya

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Institute for Computational Medicine, Johns Hopkins University)

  • Marian Novak

    (Dana-Farber Cancer Institute and Harvard Medical School
    Personal Genome Diagnostics)

  • Siân Jones

    (Personal Genome Diagnostics)

  • Jillian Phallen

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Carolyn A. Hruban

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Michelle S. Hirsch

    (Brigham and Women’s hospital and Harvard Medical School)

  • Douglas I. Lin

    (Brigham and Women’s hospital and Harvard Medical School
    Beth Israel Deaconess Medical Center)

  • Lauren Schwartz

    (University of Pennsylvania Perelman School of Medicine)

  • Cecile L. Maire

    (Dana-Farber Cancer Institute and Harvard Medical School)

  • Jean-Christophe Tille

    (Division of Clinical Pathology, Faculty of Medicine, Geneva University Hospital)

  • Michaela Bowden

    (Brigham and Women’s hospital and Harvard Medical School)

  • Ayse Ayhan

    (Seirei Mikatahara Hospital
    Hamamatsu University School of Medicine
    Hiroshima University School of Medicine
    Johns Hopkins University School of Medicine)

  • Laura D. Wood

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Robert B. Scharpf

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

  • Robert Kurman

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Tian-Li Wang

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Ie-Ming Shih

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Rachel Karchin

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
    Institute for Computational Medicine, Johns Hopkins University)

  • Ronny Drapkin

    (Dana-Farber Cancer Institute and Harvard Medical School
    Brigham and Women’s hospital and Harvard Medical School
    Penn Ovarian Cancer Research Center, University of Pennsylvania Perelman School of Medicine)

  • Victor E. Velculescu

    (Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine)

Abstract

High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease.

Suggested Citation

  • S. Intidhar Labidi-Galy & Eniko Papp & Dorothy Hallberg & Noushin Niknafs & Vilmos Adleff & Michael Noe & Rohit Bhattacharya & Marian Novak & Siân Jones & Jillian Phallen & Carolyn A. Hruban & Michell, 2017. "High grade serous ovarian carcinomas originate in the fallopian tube," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00962-1
    DOI: 10.1038/s41467-017-00962-1
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    Cited by:

    1. Elena Denisenko & Leanne Kock & Adeline Tan & Aaron B. Beasley & Maria Beilin & Matthew E. Jones & Rui Hou & Dáithí Ó Muirí & Sanela Bilic & G. Raj K. A. Mohan & Stuart Salfinger & Simon Fox & Khaing , 2024. "Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Philip Smith & Thomas Bradley & Lena Morrill Gavarró & Teodora Goranova & Darren P. Ennis & Hasan B. Mirza & Dilrini Silva & Anna M. Piskorz & Carolin M. Sauer & Sarwah Al-Khalidi & Ionut-Gabriel Funi, 2023. "The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Jennifer B. Shah & Dana Pueschl & Bradley Wubbenhorst & Mengyao Fan & John Pluta & Kurt D’Andrea & Anna P. Hubert & Jake S. Shilan & Wenting Zhou & Adam A. Kraya & Alba Llop Guevara & Catherine Ruan &, 2022. "Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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