bioRxivCancer BiologyPreprint
A patient-driven clinicogenomic partnership through the Metastatic Prostate Cancer Project
J. Crowdis, S. Balch, L. Sterlin, B. S. Thomas, S. Y. Camp, M. Dunphy, E. Anastasio, S. Shah, A. L. Damon, R. Ramos, D. M. Sosa, I. K. Small, B. Tomson, C. M. Nguyen, M. McGillicuddy, P. S. Chastain, M. X. He, A. T. M. Cheung, S. Wankowicz, A. K. Tewari, D. Kim, S. H. AlDubayan, A. Dowdye, B. Zola, J. Nowak, , E. M. Van Allen
Abstract
Molecular profiling studies have enabled numerous discoveries for metastatic prostate cancer (MPC), but they have mostly occurred in academic medical institutions focused on select patient populations. We developed the Metastatic Prostate Cancer Project (MPCproject, mpcproject.org), a patient-partnered initiative to empower MPC patients living anywhere in the U.S. and Canada to participate in molecular research and contribute directly to translational discovery. Here we present clinicogenomic results from our partnership with the first 706 MPCproject participants. We found that a patient-centered and remote research strategy enhanced engagement with patients in rural and medically underserved areas. Furthermore, patient-reported data achieved 90% consistency with abstracted health records for therapies and provided a mechanism for patient-partners to share information about their cancer experience not documented in medical records. Among the molecular profiling data from 333 patient-partners (n = 573 samples), whole exome sequencing of 63 tumor samples obtained from hospitals across the U.S. and Canada and 19 plasma cell-free DNA (cfDNA) samples from blood donated remotely recapitulated known findings in MPC and enabled longitudinal study of prostate cancer evolution. Inexpensive ultra-low coverage whole genome sequencing of 318 cfDNA samples from donated blood revealed clinically relevant genomic changes like AR amplification, even in the context of low tumor burden. Collectively, this study illustrates the power of a longitudinal partnership with patients to generate a more representative clinical and molecular understanding of MPC. NoteTo assist our patient-partners and the wider MPC community interpret the results of this study, we have included a glossary of terms in the Supplementary Materials.
- organism: human
- assay: clinical cohort / trial
- assay: DNA methylation
- assay: whole-exome sequencing
- assay: whole-genome sequencing
- research focus: cell type annotation
- research focus: variant calling
- research focus: differential expression
- research focus: gene regulatory network inference
- approach: experimental assay
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