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, Victor E Velculescu, 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, Victor E Velculescu
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.
Conflict of interest statement
V.E.V. is a founder of Personal Genome Diagnostics and is a member of its Scientific Advisory Board and Board of Directors. V.E.V. owns Personal Genome Diagnostics stock, which is subject to certain restrictions under university policy. The terms of this arrangement is managed by the Johns Hopkins University in accordance with its conflict of interest policies. The remaining authors declare no competing financial interests.
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