Functional genomics analysis reveals a MYC signature associated with a poor clinical prognosis in liposarcomas

Am J Pathol. 2015 Mar;185(3):717-28. doi: 10.1016/j.ajpath.2014.11.024. Epub 2015 Jan 23.

Abstract

Liposarcomas, which are malignant fatty tumors, are the second most common soft-tissue sarcomas. Several histologically defined liposarcoma subtypes exist, yet little is known about the molecular pathology that drives the diversity in these tumors. We used functional genomics to classify a panel of diverse liposarcoma cell lines based on hierarchical clustering of their gene expression profiles, indicating that liposarcoma gene expression profiles and histologic classification are not directly correlated. Boolean probability approaches based on cancer-associated properties identified differential expression in multiple genes, including MYC, as potentially affecting liposarcoma signaling networks and cancer outcome. We confirmed our method with a large panel of lipomatous tumors, revealing that MYC protein expression is correlated with patient survival. These data encourage increased reliance on genomic features in conjunction with histologic features for liposarcoma clinical characterization and lay the groundwork for using Boolean-based probabilities to identify prognostic biomarkers for clinical outcome in tumor patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Female
  • Genomics
  • Humans
  • Liposarcoma / genetics*
  • Liposarcoma / mortality
  • Liposarcoma / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Survival Rate
  • Transcriptome

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc