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Supplementary Table S3 from Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube

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posted on 2023-04-03, 21:02 authored by 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

Single nucleotide variants and indels.

Funding

Marsha Rivkin Foundation

National Cancer Institute

Harris Family Foundation

University of Chicago Comprehensive Cancer Center

University of Chicago Cancer Center

History

ARTICLE 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-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.Significance: We find 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. Cancer Discov; 6(12); 1342–51. ©2016 AACR.See related commentary by Swisher et al., p. 1309.This article is highlighted in the In This Issue feature, p. 1293