MSKCC Upper Tract Urothelial Carcinoma 2015

Overview

Eighty-three upper tract urothelial carcinoma (UTUC) tumors from patients treated with radical nephroureterectomy at Memorial Sloan Kettering Cancer Center, sequenced with the MSK-IMPACT 300-gene hybrid-capture panel. At the time of publication, this represented the largest NGS-profiled UTUC cohort. The dataset is publicly available through the MSKCC cBioPortal for Cancer Genomics. A high-grade UCB comparator cohort (n=102; study blca_mskcc_solit_2014) was profiled on the same platform.

Composition

  • Cancer types: UTUC (upper tract urothelial carcinoma); all primary urothelial histology, no predominant variants.
  • Sample count: 83 tumors (60 high-grade, 23 low-grade); all obtained at radical nephroureterectomy.
  • Clinical fields: tumor grade, T stage, smoking history, age, sex, history of UTUC.
  • Sequencing: MSK-IMPACT 300-gene custom hybrid-capture panel, Illumina HiSeq 2500; mean coverage 650× (UTUC cohort); reference genome hg19.
  • Variant calling: BWA v0.6.2, MuTect v1.0.27783 (SNVs), SomaticIndelDetector (indels), DELLY (structural rearrangements). Orthogonal validation with MiSeq and Sanger sequencing (100% concordance for 10-gene re-test).
  • Patient demographics: median age 70 yr (IQR 63–76); matched to the UCB comparator cohort on age, sex, smoking, and stage distributions.

Assays / panels (linked)

Papers using this cohort

  • PMID:26278805 — Sfakianos et al. 2015, “Genomic Characterization of Upper Tract Urothelial Carcinoma,” European Urology.

Notable findings derived from this cohort

  • UTUC and UCB share the same gene catalog but differ in prevalence: UTUC enriched for FGFR3 (35.6% vs 21.6%), HRAS (13.6% vs 1.0%, p=0.001), and CDKN2B deletions (15.3% vs 3.9%), while UCB enriched for TP53 (25.4% vs 57.8%, p<0.001) and RB1 (0% vs 18.6%, p<0.001) alterations PMID:26278805.
  • First description of a POLE V411L ultramutated urothelial tumor (422 somatic mutations) in UTUC; five intrachromosomal FGFR3-TACC3 fusions identified exclusively in high-grade UTUC (8.5% vs 2.0% in UCB) PMID:26278805.
  • 22/23 low-grade UTUC tumors (96%) harbored activating FGFR3 mutations; all 23 were TP53 and RB1 wild-type, supporting a low-grade-tumor-progression model distinct from de novo high-grade UCB PMID:26278805.

Sources

  • cBioPortal study: utuc_mskcc_2015

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