• Mark A Eckert, Shawn Pan, Kyle M Hernandez, Rachel M Loth, Jorge Andrade, Samuel L Volchenboum, Pieter Faber, Anthony Montag, Ricardo Lastra, Marcus E Peter, S Diane Yamada, and Ernst Lengyel.
• Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois.
• Cancer Discov. 2016 Dec 1; 6 (12): 1342-1351.

AbstractAccumulating evidence has supported the fallopian tube rather than the ovary as the origin for high-grade serous ovarian cancer (HGSOC). To understand the relationship between putative precursor lesions and metastatic tumors, we performed whole-exome sequencing on specimens from eight HGSOC patient progression series consisting of serous tubal intraepithelial carcinomas (STIC), invasive fallopian tube lesions, invasive ovarian lesions, and omental metastases. Integration of copy number and somatic mutations revealed patient-specific patterns with similar mutational signatures and copy-number variation profiles across all anatomic sites, suggesting that genomic instability is an early event in HGSOC. Phylogenetic analyses supported STIC as precursor lesions in half of our patient cohort, but also identified STIC as metastases in 2 patients. Ex vivo assays revealed that HGSOC spheroids can implant in the fallopian tube epithelium and mimic STIC lesions. That STIC may represent metastases calls into question the assumption that STIC are always indicative of primary fallopian tube cancers.©2016 American Association for Cancer Research.

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