TY - JOUR
T1 - High grade serous ovarian carcinomas originate in the fallopian tube
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.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85032176462
UR - https://www.scopus.com/pages/publications/85032176462#tab=citedBy
U2 - 10.1038/s41467-017-00962-1
DO - 10.1038/s41467-017-00962-1
M3 - Article
C2 - 29061967
AN - SCOPUS:85032176462
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1093
ER -