Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets

BMC Med Genet. 2018 Dec 31;19(Suppl 1):216. doi: 10.1186/s12881-018-0722-6.

Abstract

Background: Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling.

Results: The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy.

Conclusions: This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy.

Keywords: CDK4 and RB1; Complex karyotype sarcoma; Molecular characterization; PDGFRA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 4 / genetics*
  • Cyclin-Dependent Kinase 4 / metabolism
  • DNA Copy Number Variations
  • Exome Sequencing
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Karyotyping
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Retinoblastoma Binding Proteins / genetics*
  • Retinoblastoma Binding Proteins / metabolism
  • Retrospective Studies
  • Sarcoma / drug therapy
  • Sarcoma / genetics*
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / drug therapy
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / metabolism
  • Soft Tissue Neoplasms / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism
  • X-linked Nuclear Protein / genetics
  • X-linked Nuclear Protein / metabolism

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases
  • Receptor, Platelet-Derived Growth Factor alpha
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • ATRX protein, human
  • X-linked Nuclear Protein