High grade serous ovarian carcinomas originate in the fallopian tube

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 n...

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Vydáno v:Nature communications Ročník 8; číslo 1; s. 1093 - 11
Hlavní autoři: 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 D., Scharpf, Robert B., Kurman, Robert, Wang, Tian-Li, Shih, Ie-Ming, Karchin, Rachel, Drapkin, Ronny, Velculescu, Victor E.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 23.10.2017
Nature Publishing Group
Nature Portfolio
Témata:
631/67/1517/1709
631/67/69
Aberration
Alleles
BRCA1 protein
BRCA2 protein
Breast cancer
Cancer
Copy number
Cystadenocarcinoma, Serous - genetics
DNA Copy Number Variations - genetics
Etiology
Evolution
Fallopian tube
Fallopian Tube Neoplasms - metabolism
Fallopian Tube Neoplasms - pathology
Fallopian Tubes - metabolism
Fallopian Tubes - pathology
Female
Genital cancers
Gynecological cancer
Humanities and Social Sciences
Humans
Immunohistochemistry
Laser Capture Microdissection
Lesions
Metastases
Metastasis
multidisciplinary
Neoplasms, Cystic, Mucinous, and Serous - metabolism
Neoplasms, Cystic, Mucinous, and Serous - pathology
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
p53 Protein
Patients
PTEN protein
Science
Science (multidisciplinary)
Signatures
ISSN:2041-1723, 2041-1723
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Shrnutí: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. It has previously been proposed that high-grade serous ovarian carcinoma (HGSOC) may originate from the fallopian tube. Here, the authors analyze genetic aberrances in fallopian tube lesions, ovarian cancers, and metastases from HGSOC patients and establish the evolutionary origins of HGSOC in the fallopian tube.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-00962-1