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

doi:10.1038/s41467-017-00962-1

High grade serous ovarian carcinomas originate in the fallopian tube

Nat Commun. 2017 Oct 23;8(1):1093. doi: 10.1038/s41467-017-00962-1.

Authors

S Intidhar Labidi-Galy^{1

2}, Eniko Papp^{3

4}, Dorothy Hallberg³, Noushin Niknafs^{3

5}, Vilmos Adleff³, Michael Noe³, Rohit Bhattacharya^{3

6}, Marian Novak^{1

4}, Siân Jones⁴, Jillian Phallen³, Carolyn A Hruban³, Michelle S Hirsch⁷, Douglas I Lin^{7

8}, Lauren Schwartz⁹, Cecile L Maire¹, Jean-Christophe Tille¹⁰, Michaela Bowden⁷, Ayse Ayhan^{11

12

13

14}, Laura D Wood³, Robert B Scharpf³, Robert Kurman^{3

14}, Tian-Li Wang^{3

14}, Ie-Ming Shih^{3

14}, Rachel Karchin^{3

5}, Ronny Drapkin^{15

16

17}, Victor E Velculescu¹⁸

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 02215, USA.
² Department of Oncology, Geneva University Hospitals, Geneva, 1205, Switzerland.
³ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁴ Personal Genome Diagnostics, Baltimore, MD, 21224, USA.
⁵ Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁶ Department of Computer Science, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁷ Department of Pathology, Brigham and Women's hospital and Harvard Medical School, Boston, MA, 02115, USA.
⁸ Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
⁹ Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
¹⁰ Division of Clinical Pathology, Faculty of Medicine, Geneva University Hospital, 1205, Geneva, Switzerland.
¹¹ Department of Pathology, Seirei Mikatahara Hospital, Hamamatsu, 433-8558, Japan.
¹² Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
¹³ Department of Molecular Pathology, Hiroshima University School of Medicine, Hiroshima, 739-0046, Japan.
¹⁴ Departments of Gynecology and Obstetrics and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
¹⁵ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 02215, USA. rdrapkin@pennmedicine.upenn.edu.
¹⁶ Department of Pathology, Brigham and Women's hospital and Harvard Medical School, Boston, MA, 02115, USA. rdrapkin@pennmedicine.upenn.edu.
¹⁷ Department of Obstetrics and Gynecology, Penn Ovarian Cancer Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. rdrapkin@pennmedicine.upenn.edu.
¹⁸ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. velculescu@jhmi.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Cystadenocarcinoma, Serous / genetics*
DNA Copy Number Variations / genetics
Fallopian Tube Neoplasms / metabolism
Fallopian Tube Neoplasms / pathology*
Fallopian Tubes / metabolism
Fallopian Tubes / pathology*
Female
Humans
Immunohistochemistry
Laser Capture Microdissection
Neoplasms, Cystic, Mucinous, and Serous / metabolism
Neoplasms, Cystic, Mucinous, and Serous / pathology*
Ovarian Neoplasms / genetics*

Abstract

Publication types

MeSH terms

Grants and funding