High grade serous ovarian carcinomas originate in the fallopian tube

Sana Intidhar Labidi‐Galy(Harvard University), Eniko Papp(Human Genome Sciences (United States)), Dorothy Hallberg(Johns Hopkins University), Noushin Niknafs(Johns Hopkins University), Vilmos Adleff(Johns Hopkins University), Michaël Noë(Johns Hopkins University), Rohit Bhattacharya(Johns Hopkins University), Marián Novak(Human Genome Sciences (United States)), Siân Jones(Human Genome Sciences (United States)), Jillian Phallen(Johns Hopkins University), Carolyn Hruban(Johns Hopkins University), Michelle S. Hirsch(Brigham and Women's Hospital), Douglas I. Lin(Brigham and Women's Hospital), Lauren E. Schwartz(University of Pennsylvania), Cécile L. Maire(Harvard University), Jean‐Christophe Tille(University Hospital of Geneva), Michaela Bowden(Brigham and Women's Hospital), A. Ayhan(Hiroshima University), Laura D. Wood(Johns Hopkins University), Robert B. Scharpf(Johns Hopkins University), Robert J. Kurman(Johns Hopkins University), Tian-Li Wang(Johns Hopkins University), Ie‐Ming Shih(Johns Hopkins University), Rachel Karchin(Johns Hopkins University), Ronny Drapkin(Brigham and Women's Hospital), Victor E. Velculescu(Johns Hopkins University)
Nature Communications
October 17, 2017
10.1038/s41467-017-00962-1
Cited by 756Open Access
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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.

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