MSK Paired Bladder Cancer Primary-Metastasis Study (2022)

Overview

Institutional cohort from Memorial Sloan Kettering Cancer Center profiling 1,313 patients with bladder urothelial carcinoma by MSK-IMPACT (prospectively enrolled 2014–2021). The study includes 119 matched primary-metastasis tumor pairs sequenced by MSK-IMPACT targeted sequencing, 22 pairs sequenced by whole-exome sequencing, and 123 patients with at least one tumor sample and paired plasma cfDNA via MSK-ACCESS (~20,000x raw coverage, ~1,000x duplex). The dataset is publicly available on cBioPortal as paired_bladder_2022.

Composition

  • 1,313 patients with BLCA or UTUC prospectively sequenced at MSK.
  • 119 matched primary-metastasis pairs by MSK-IMPACT; 22 pairs by WES (tumor purity >=25% by FACETS).
  • 45 patients with primary tumor, metastasis, and plasma cfDNA; 123 patients with at least one tumor sample and cfDNA.
  • Key clinical fields: grade, stage, tumor site, lines of prior therapy, time between primary and metastatic sample collection (median 10.5 months, IQR 2.6–25.5).

Assays / panels (linked)

  • MSK-IMPACT — targeted tumor-normal sequencing
  • whole-exome-seq — 22 primary-metastasis pairs
  • MSK-ACCESS — plasma cfDNA (~20,000x raw, ~1,000x duplex)
  • FACETS — allele-specific copy number and tumor purity estimation

Papers using this cohort

  • PMID:36543146 — Clinton et al., Cell Reports 2022. Genomic heterogeneity as a barrier to precision oncology in urothelial cancer.

Notable findings derived from this cohort

  • Mean mutational concordance by WES between primary and metastatic tumors was only 42% (range 6%–84%), consistent with early branched evolution; 23% of potentially actionable gene mutations (FGFR3, PIK3CA, TSC1, ERBB2) were discordant between paired sites PMID:36543146.
  • ARID1A mutations, when discordant between primary and metastatic sites, were always exclusive to the metastatic sample (16% of ARID1A-mutant patients), suggesting late acquisition during metastatic progression PMID:36543146.
  • ERBB2 showed the highest discordance rate (38%) among targetable genes, followed by PIK3CA (27%), TSC1 (17%), and FGFR3 (9%) PMID:36543146.
  • Plasma cfDNA by MSK-ACCESS identified 17% of targetable alterations (60% concordant, 17% cfDNA-exclusive, 23% tissue-exclusive) and detected convergent evolution with 4 distinct oncogenic FGFR3 alterations in one patient during erdafitinib therapy PMID:36543146.

Sources

  • cBioPortal study: paired_bladder_2022
  • Associated publication: PMID:36543146

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