Pleomorphic Liposarcoma (PLLS)

Overview

Pleomorphic liposarcoma (PLLS) is the rarest and most aggressive liposarcoma subtype, characterized by sheets of pleomorphic lipoblasts without the MDM2/CDK4 amplification that defines well-differentiated/dedifferentiated liposarcoma. On OncoTree it is a child of LIPO (Liposarcoma) under Soft Tissue. Barretina et al. identified TP53 mutation and NF1 inactivation as recurrent drivers; PLLS shares a strikingly similar genomic profile with MFS, suggesting a unified molecular class.

Cohorts in the corpus

  • sarc_mskcc: 24 PLLS patients (11.6% of 207 high-grade STS), profiled by targeted resequencing (722 genes), 250K SNP-array SCNA, LOH, and expression arrays. PMID:20601955

Recurrent alterations

  • TP53 — mutated in 17% of PLLS; the only subtype in the seven-subtype cohort in which TP53 mutations were detected. PMID:20601955
  • NF1 — mutated in 8% of PLLS (point mutations + genomic deletions); biallelic inactivation observed in some tumors; loss linked to mTOR pathway activation. First report of somatic NF1 alterations outside MPNST/GIST in the context of NF1 patients. PMID:20601955
  • RB1 — mutation identified in PLLS; consistent with broader Rb pathway implication in CDK4-dependent sarcomas. PMID:20601955
  • ERBB4 — mutations found on resequencing of PLLS and MFS samples. PMID:20601955
  • PTEN — splice-site mutation identified in PLLS. PMID:20601955
  • Complex karyotype: PLLS and MFS are genomically similar (copy-number complexity, copy-neutral LOH), supporting a unified molecular class; distinct from the myxoid/round-cell and synovial sarcoma clusters. PMID:20601955

Subtypes

  • Genomically clusters with MFS — both show complex karyotypes with overlapping driver alterations (NF1, TP53, ERBB4); may represent a unified molecular class despite distinct histology. PMID:20601955

Therapeutic landscape

  • mTOR inhibition proposed for NF1-deficient PLLS: NF1 loss activates the RAS–mTOR axis, providing a rationale for rapalogs. PMID:20601955

Sources

  • PMID:20601955 — Barretina et al. Nature 2010. Integrative genomic analysis of 207 high-grade soft tissue sarcomas across seven subtypes (MSKCC Sarcoma Genome Project).

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