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

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. ScharpfRobert Kurman, Tian Li Wang, Ie Ming Shih, Rachel Karchin, Ronny Drapkin, Victor E. Velculescu

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215 Scopus citations

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.

Original language	English (US)
Article number	1093
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00962-1
State	Published - Dec 1 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Labidi-Galy, S. I., Papp, E., Hallberg, D., Niknafs, N., Adleff, V., Noe, M., Bhattacharya, R., Novak, M., Jones, S., Phallen, J., Hruban, C. A., Hirsch, M. S., Lin, D. I., Schwartz, L., Maire, C. L., Tille, J. C., Bowden, M., Ayhan, A., Wood, L. D., ... Velculescu, V. E. (2017). High grade serous ovarian carcinomas originate in the fallopian tube. Nature communications, 8(1), Article 1093. https://doi.org/10.1038/s41467-017-00962-1

Labidi-Galy, SI, Papp, E, Hallberg, D, Niknafs, N , Adleff, V, Noe, M, Bhattacharya, R, Novak, M, Jones, S, Phallen, J, Hruban, CA, Hirsch, MS, Lin, DI, Schwartz, L, Maire, CL, Tille, JC, Bowden, M, Ayhan, A, Wood, LD , Scharpf, RB , Kurman, R , Wang, TL , Shih, IM , Karchin, R, Drapkin, R & Velculescu, VE 2017, 'High grade serous ovarian carcinomas originate in the fallopian tube', Nature communications, vol. 8, no. 1, 1093. https://doi.org/10.1038/s41467-017-00962-1

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title = "High grade serous ovarian carcinomas originate in the fallopian tube",

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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AU - Labidi-Galy, S. Intidhar

AU - Papp, Eniko

AU - Hallberg, Dorothy

AU - Niknafs, Noushin

AU - Adleff, Vilmos

AU - Noe, Michael

AU - Bhattacharya, Rohit

AU - Novak, Marian

AU - Jones, Siân

AU - Phallen, Jillian

AU - Hruban, Carolyn A.

AU - Hirsch, Michelle S.

AU - Lin, Douglas I.

AU - Schwartz, Lauren

AU - Maire, Cecile L.

AU - Tille, Jean Christophe

AU - Bowden, Michaela

AU - Ayhan, Ayse

AU - Wood, Laura D.

AU - Scharpf, Robert B.

AU - Kurman, Robert

AU - Wang, Tian Li

AU - Shih, Ie Ming

AU - Karchin, Rachel

AU - Drapkin, Ronny

AU - Velculescu, Victor E.

PY - 2017/12/1

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N2 - 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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High grade serous ovarian carcinomas originate in the fallopian tube

Abstract

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