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 Delong Wood, Robert B Scharpf & 6 others Robert J Kurman, Tian-Li Wang, Ie Ming Shih, Rachel Karchin, Ronny Drapkin, Victor E Velculescu

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number1093
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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Fallopian Tubes
Carcinoma in Situ
Tumors
grade
cancer
Ovarian Neoplasms
tubes
Carcinoma
Lasers
Fallopian Tube Neoplasms
Neoplasm Metastasis
Exome
metastasis
signatures
etiology
Neoplasms
lesions

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

High grade serous ovarian carcinomas originate in the fallopian tube. / Labidi-Galy, S. Intidhar; Papp, Eniko; Hallberg, Dorothy; Niknafs, Noushin; Adleff, Vilmos; Noe, Michael; Bhattacharya, Rohit; Novak, Marian; Jones, Siân; Phallen, Jillian; Hruban, Carolyn A.; Hirsch, Michelle S.; Lin, Douglas I.; Schwartz, Lauren; Maire, Cecile L.; Tille, Jean Christophe; Bowden, Michaela; Ayhan, Ayse; Wood, Laura Delong; Scharpf, Robert B; Kurman, Robert J; Wang, Tian-Li; Shih, Ie Ming; Karchin, Rachel; Drapkin, Ronny; Velculescu, Victor E.

In: Nature Communications, Vol. 8, No. 1, 1093, 01.12.2017.

Research output: Contribution to journalArticle

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, RJ, Wang, T-L, 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
Labidi-Galy, S. Intidhar ; Papp, Eniko ; Hallberg, Dorothy ; Niknafs, Noushin ; Adleff, Vilmos ; Noe, Michael ; Bhattacharya, Rohit ; Novak, Marian ; Jones, Siân ; Phallen, Jillian ; Hruban, Carolyn A. ; Hirsch, Michelle S. ; Lin, Douglas I. ; Schwartz, Lauren ; Maire, Cecile L. ; Tille, Jean Christophe ; Bowden, Michaela ; Ayhan, Ayse ; Wood, Laura Delong ; Scharpf, Robert B ; Kurman, Robert J ; Wang, Tian-Li ; Shih, Ie Ming ; Karchin, Rachel ; Drapkin, Ronny ; Velculescu, Victor E. / High grade serous ovarian carcinomas originate in the fallopian tube. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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AU - Adleff, Vilmos

AU - Noe, Michael

AU - Bhattacharya, Rohit

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AU - Jones, Siân

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AU - Hruban, Carolyn A.

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AU - Maire, Cecile L.

AU - Tille, Jean Christophe

AU - Bowden, Michaela

AU - Ayhan, Ayse

AU - Wood, Laura Delong

AU - Scharpf, Robert B

AU - Kurman, Robert J

AU - Wang, Tian-Li

AU - Shih, Ie Ming

AU - Karchin, Rachel

AU - Drapkin, Ronny

AU - Velculescu, Victor E

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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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