Prostate Cancer (MSK, 2024)
Overview
Large single-center retrospective cohort of 2,257 prostate cancer (PRAD) patients treated at Memorial Sloan Kettering Cancer Center from April 2015 to February 2021, with 3,244 tumors sequenced by MSK-IMPACT. Designed to characterize MSI-H/dMMR and TMB-H/MSS prostate cancers and evaluate their response to immune checkpoint blockade. Data deposited in cBioPortal as prostate_msk_2024. PMID:38949888
Composition
- 2,257 patients; 3,244 tumors sequenced with MSK-IMPACT. PMID:38949888
- MSI-H/dMMR: 63 (2.8%); TMB-H/MSS: 33 (1.5%); TMB-L/MSS: 2,161 (95.7%). PMID:38949888
- WES performed on 48 tumor samples (20 MSI-H/dMMR, 28 TMB-H/MSS) via recapture of MSK-IMPACT libraries. PMID:38949888
Assays / panels (linked)
- MSK-IMPACT targeted NGS. PMID:38949888
- Whole-exome sequencing (WES) on selected samples. PMID:38949888
- FACETS (v0.5.6) for copy-number analysis. PMID:38949888
- MSIsensor (v0.5) for MSI status; TMB defined as non-synonymous mutations per megabase in canonical exons. PMID:38949888
Papers using this cohort
- PMID:38949888 — Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.
Notable findings derived from this cohort
- MSI-H/dMMR tumors had significantly higher TMB than TMB-H/MSS (median 41 vs. 15 mut/Mb, P<0.01). Both MSI-H/dMMR (62%) and TMB-H/MSS (59%) tumors more commonly Gleason grade group 5. PMID:38949888
- ICB response in MSI-H/dMMR (n=27): 45% RECIST ORR (including 2 CRs, 7 PRs); 65% PSA50 response. In TMB-H/MSS (n=8): 0% RECIST response; 50% PSA50 response. PMID:38949888
- Median rPFS tended to favor MSI-H/dMMR vs. TMB-H/MSS (38 vs. 7 months, HR 2.13, P=0.14). PMID:38949888
- WES: MSI-H/dMMR tumors had significantly higher neoantigen burden (11.1 vs. 6.8, P=0.011) and indel burden vs. TMB-H/MSS. PMID:38949888
Sources
- cBioPortal study
prostate_msk_2024PMID:38949888.
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