RT Journal Article
SR Electronic
T1 Extensive Intratumor Proteogenomic Heterogeneity Revealed by Multiregion Sampling in a High-Grade Serous Ovarian Tumor Specimen
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 761155
DO 10.1101/761155
A1 Allison L. Hunt
A1 Nicholas W. Bateman
A1 Brian L. Hood
A1 Kelly A. Conrads
A1 Ming Zhou
A1 Tracy J. Litzi
A1 Julie Oliver
A1 Dave Mitchell
A1 Glenn Gist
A1 Brian Blanton
A1 Kunle Odunsi
A1 Anil K. Sood
A1 Yovanni Casablanca
A1 Kathleen M. Darcy
A1 Craig D. Shriver
A1 Uma N. M. Rao
A1 G. Larry Maxwell
A1 Thomas P. Conrads
YR 2019
UL http://biorxiv.org/content/early/2019/09/08/761155.abstract
AB A series of 200 consecutive thin sections were generated from a high-grade serous ovarian tumor and laser microdissected four spatially separated “core” regions of tumor epithelium, along with tumor epithelium, stroma or whole tissue harvests at 200 μm intervals. These distinct tissue collections were analyzed by quantitative proteomics and RNA-Seq. Unsupervised analyses revealed co-clustering of tumor cores with enriched tumor epithelium, which were distinct from the enriched stroma and whole tumor collections. Strong correlations in protein and transcript abundance in tumor epithelium and stromal collections from neighboring thin sections were decreased in samples harvested just hundreds of microns apart. Stroma (mesenchymal) and tumor epithelium (differentiated) displayed a distinct association with ovarian cancer prognostic molecular sub-types with a 2-year difference in median survival. These data reveal substantial tumor microenvironment protein and transcript expression heterogeneity that directly bear on prognostic signatures and underscore the need to enrich cellular subpopulations for expression profiling.