Dana-Farber / MSKCC Bladder Urothelial Carcinoma Cisplatin Response (2014)

Overview

50-patient extreme-phenotype cohort of muscle-invasive urothelial carcinoma (BLCA) collected under Dana-Farber protocols 02-021/11-334 and MSKCC protocols 89-076/09-025. Cases were selected for neoadjuvant cisplatin-based chemotherapy followed by cystectomy, balanced 25 responders (pT0/pTis) vs. 25 non-responders (residual ≥pT2). Pre-treatment tumor and paired germline DNA were sequenced by whole-exome sequencing at mean 121× tumor / 130× germline coverage (hg19).

Composition

• 50 patients; 25 cisplatin responders (no residual invasive disease), 25 non-responders (residual ≥pT2 disease).
• Cancer type: BLCA.
• Assay: whole-exome-seq (SureSelect v2, Illumina HiSeq); orthogonal amplicon validation by Fluidigm Access Array / MiSeq (35/50 cases).
• Variant calling: mutect (SNVs), indelocator (indels), significance by mutsig (MutSigCV).

Assays / panels (linked)

• whole-exome-seq

Papers using this cohort

• PMID:25096233

Notable findings derived from this cohort

• ERCC2 somatic mutations were found exclusively in cisplatin responders (9/25, 36% vs. 0/25 non-responders; q = 0.007), proposing ERCC2 as a predictive biomarker for cisplatin sensitivity in muscle-invasive urothelial carcinoma PMID:25096233.
• Responders had significantly higher median mutation rate (9.7 vs 4.4 mutations/Mb; P = 0.0003); MutSigCV nominated TP53, RB1, KDM6A, and ARID1A as significantly mutated across the full cohort PMID:25096233.

Sources

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