Broad/DFCI Cutaneous Melanoma WGS (skcm_broad_dfarber)

Overview

The Broad/DFCI melanoma WGS dataset comprises 25 metastatic cutaneous melanomas with matched germline DNA, sequenced at 59-fold tumor and 32-fold normal haploid coverage. Sequencing used Illumina GAIIx (5 cases) and Illumina HiSeq 2000 (20 cases) with paired-end 101-nt reads aligned to hg19 with BWA. An extension cohort of 107 tumor/normal pairs (45 tumors + 62 short-term cultures) was screened by bidirectional Sanger sequencing of 40 PREX2 exons. Data are available at dbGaP (phs000452.v1.p1).

Composition

  • 25 metastatic cutaneous melanoma/germline pairs (discovery)
  • 107 tumor/normal pairs (extension cohort; Sanger sequencing of PREX2 exons)
  • Cancer type: SKCM (includes 2 acral and 23 trunk/non-acral melanomas)
  • Somatic mutation rates varied nearly 100-fold (acral: 3-14/Mb; trunk: 5-55/Mb; hypermutated: 111/Mb)

Assays / panels (linked)

Papers using this cohort

Notable findings derived from this cohort

  • PREX2 was recurrently mutated in 11/25 discovery tumors and 14% of the 107-sample extension cohort; truncated and point-mutant PREX2 variants accelerated in vivo tumor formation in PMEL-NRAS* melanocytes PMID:22622578
  • BRAF V600E present in 16/25 tumors (64%); NRAS mutated in 9/25 (36%); BRAF and NRAS mutations were mutually exclusive PMID:22622578
  • Average of 97 structural rearrangements per genome (range 6-420); chromothripsis observed in select tumors; recurrently rearranged genes include PTEN (4), FHIT (6), MACROD2 (5) PMID:22622578
  • C>T transitions consistent with UV mutagenesis dominated high-mutation-rate tumors (93% in hypermutated ME009 vs. 36% in acral ME015) PMID:22622578

Sources

This page was processed by entity-page-writer on 2026-05-06.