Journal
JCI INSIGHT
Volume 2, Issue 17, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.95703
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Funding
- NIH [P30CA047904]
- University of Pittsburgh Center for Research Computing
- University of Pittsburgh Center for Simulation and Modeling
- Susan G. Komen Scholar awards [SAC110021, SAC160073]
- Breast Cancer Research Foundation
- Magee-Womens Research Institute and Foundation
- Nicole Meloche Foundation
- Penguins Foundation
- Penguins Alumni Foundation
- Mario Lemieux Foundation
- Department of Defense [BC123242]
- NIH/National Institute of General Medical Sciences [2T32GM008424-21]
- NIH/National Cancer Institute [5F30CA203095]
- [Fashion Footwear Association of New York]
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Bone metastases (BoM) are a significant cause of morbidity in patients with estrogen receptor-positive (ER-positive) breast cancer; yet, characterizations of human specimens are limited. In this study, exome-capture RNA sequencing (ecRNA-seq) on aged (8-12 years), formalin-fixed, paraffin-embedded (FFPE), and decalcified cancer specimens was evaluated. Gene expression values and ecRNA-seq quality metrics from FFPE or decalcified tumor RNA showed minimal differences when compared with matched flash-frozen or nondecalcified tumors. ecRNA-seq was then applied on a longitudinal collection of 11 primary breast cancers and patient-matched synchronous or recurrent BoMs. Overtime, BoMs exhibited gene expression shifts to more Her2 and LumB PAM50 subtype profiles, temporally influenced expression evolution, recurrently dysregulated prognostic gene sets, and longitudinal expression alterations of clinically actionable genes, particularly in the CDK/Rb/E2F and FGFR signaling pathways. Taken together, this study demonstrates the use of ecRNA-seq on decade-old and decalcified specimens and defines recurrent longitudinal transcriptional remodeling events in estrogen-deprived breast cancers.
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