Skin Cutaneous Melanoma (Broad, Cell 2012)

Overview

The Broad melanoma dataset comprises 121 qualified melanoma tumor/normal pairs from 135 patients profiled by whole-exome sequencing. The study (Hodis et al., Cell 2012) focused on SKCM (cutaneous melanoma) with representation from multiple sample types (primary tumors, metastatic samples, short-term cultures from metastatic tissue). The cohort was used to discover six novel melanoma driver genes using the InVEx permutation statistical framework, which accounts for the high UV-induced somatic mutation background characteristic of melanoma.

Composition

  • 121 qualified tumor/normal pairs from 135 melanoma patients
  • Subtypes: 95 cutaneous, 5 acral, 2 mucosal, 1 uveal, 18 unknown primary
  • Sample types: 15 primary tumors, 30 metastatic, 76 short-term cultures from metastatic tissue
  • Validation extension sets: n=59, n=63, and n=175 additional melanoma samples (Sequenom genotyping)
  • Cancer type: SKCM, MEL

Assays / panels (linked)

Papers using this cohort

Notable findings derived from this cohort

  • Median somatic mutation rate 14.4 coding mutations/Mb (highest of any tumor type at the time); 82.2% UV-signature C>T transitions PMID:22817889
  • Six novel significantly mutated melanoma genes identified: PPP6C, RAC1, SNX31, TACC1, STK19, ARID2 PMID:22817889
  • RAC1 P29S validated as gain-of-function, UV-induced driver at 3.9% prevalence across discovery + extension sets (14/355 patients) PMID:22817889
  • 83% of samples had hotspot BRAF or NRAS mutations (mutually exclusive, p=3e-14); PTEN loss co-occurred with BRAF (44%) but rarely with NRAS (4%) PMID:22817889
  • NF1 loss-of-function enriched in BRAF/NRAS-WT melanomas (25% vs 2%, p=5.8e-3) PMID:22817889

Sources

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