Genomics of ovarian cancer progression reveals diverse metastatic trajectories including intraepithelial metastasis to the fallopian tube

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, Ernst Lengyel*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Accumulating 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-specifi c patterns with similar mutational signatures and copy-number variation profi les 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 identifi ed 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. SIGNIFICANCE: We fi nd that the putative precursor lesions for HGSOC, STIC, possess most of the genomic aberrations present in advanced cancers. In addition, a proportion of STIC represent intraepithelial metastases to the fallopian tube rather than the origin of HGSOC.

Original languageEnglish (US)
Pages (from-to)1342-1351
Number of pages10
JournalCancer discovery
Volume6
Issue number12
DOIs
StatePublished - Dec 2016

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Genomics of ovarian cancer progression reveals diverse metastatic trajectories including intraepithelial metastasis to the fallopian tube'. Together they form a unique fingerprint.

  • Cite this

    Eckert, M. A., Pan, S., Hernandez, K. M., Loth, R. M., Andrade, J., Volchenboum, S. L., Faber, P., Montag, A., Lastra, R., Peter, M. E., Yamada, S. D., & Lengyel, E. (2016). Genomics of ovarian cancer progression reveals diverse metastatic trajectories including intraepithelial metastasis to the fallopian tube. Cancer discovery, 6(12), 1342-1351. https://doi.org/10.1158/2159-8290.CD-16-0607