Nature communications · 2017
High grade serous ovarian carcinomas originate in the fallopian tube.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.