High grade serous ovarian carcinomas originate in the fallopian tube

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, Michelle S. Hirsch, Douglas I. Lin, Lauren Schwartz, Cecile L. Maire, Jean-Christophe Tille, Michaela Bowden, Ayse Ayhan, Laura D. Wood, Robert B. Scharpf, Robert Kurman, Tian-Li Wang, Ie-Ming Shih, Rachel Karchin, Ronny Drapkin () and Victor E. Velculescu ()
Additional contact information
S. Intidhar Labidi-Galy: Dana-Farber Cancer Institute and Harvard Medical School
Eniko Papp: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
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
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
Marian Novak: Dana-Farber Cancer Institute and Harvard Medical School
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
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
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
Tian-Li Wang: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Ie-Ming Shih: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Rachel Karchin: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Ronny Drapkin: Dana-Farber Cancer Institute and Harvard Medical School
Victor E. Velculescu: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00962-1

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