MSKCC Sarcoma Genome Project

Overview

The MSKCC Sarcoma Genome Project (sarc_mskcc) is an integrative genomic study of 207 high-grade soft tissue sarcomas across seven major subtypes, generated at Memorial Sloan Kettering Cancer Center. Raw data were deposited in NCBI GEO under accession GSE21124. The study was published in 2010 and aimed to identify subtype-specific genomic drivers to inform targeted therapy in sarcoma. PMID:20601955

Composition

• 207 patients with high-grade soft tissue sarcoma across seven subtypes: DDLS (n=50, 24.2%), MRLS (n=21, 10.1%), PLLS (n=24, 11.6%), LMS (n=27, 13%), GIST (n=22, 10.6%), MFS (n=38, 18.4%), SYNS (n=24, 11.6%). PMID:20601955
• Targeted resequencing performed on 47 tumor/normal pairs; extended genotyping on 160 additional tumors via sequenom-genotyping. PMID:20601955
• Somatic copy-number alterations profiled via affymetrix-250k-snp-array (n=207); LOH analysis (n=200); oligonucleotide expression arrays (n=149). PMID:20601955

Assays / panels (linked)

• affymetrix-250k-snp-array — genome-wide copy-number and LOH profiling (n=207)
• sequenom-genotyping — extended targeted genotyping of 160 additional tumors
• gistic — statistical analysis of significant copy-number alterations
• shrna-rnai-screen — functional screen of 385 genes (2,007 shRNAs) in three DDLS cell lines

Papers using this cohort

• PMID:20601955 — Barretina et al. (2010), “Subtype-specific genomic alterations define new targets for soft tissue sarcoma therapy,” Nature Genetics.

Notable findings derived from this cohort

• TP53 mutated in 17% of PLLS; the only subtype in this cohort with TP53 mutations detected. PMID:20601955
• NF1 mutated in 10.5% of MFS and 8% of PLLS via point mutations and genomic deletions; biallelic inactivation observed; first report of somatic NF1 alteration outside MPNST/GIST in NF1 patients. PMID:20601955
• PIK3CA mutated in 18% (13/71) of MRLS; helical-domain mutations (E542K, E545K) associated with AKT activation and shorter disease-specific survival (log-rank p=0.036). PMID:20601955
• Chromosome 12q amplification found in ~90% of DDLS, encompassing CDK4, MDM2, and YEATS4 as functionally validated therapeutic targets. PMID:20601955
• CDK4 identified as top dependency in DDLS via shRNA screen; pharmacologic inhibition with palbociclib (PD0332991) induced G1 arrest. PMID:20601955
• MRLS, SYNS, and GIST had relatively simple karyotypes; DDLS, PLLS, LMS, and MFS had complex genomic landscapes. PMID:20601955

Sources

• NCBI GEO accession: GSE21124
• cBioPortal study: sarc_mskcc
• Primary publication: PMID:20601955

This page was processed by crosslinker on 2026-05-04.