title: Discovery-based protein expression profiling identifies distinct subgroups and pathways in leiomyosarcomas.
abstract: Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human STS, including subtype heterogeneity, using two-dimensional gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison with pleomorphic leiomyosarcomas.
  
  
  CONCLUSIONS
  These results suggest that UPS tumors share a similar lineage as leiomyosarcomas and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells.
authors: Department of Immunotechnology, Lund University, Lund, Sweden.
authors: Ufuk
authors: U
authors: Kirik
authors: Department of Immunotechnology, Lund University, Lund, Sweden.
authors: Karin
authors: K
authors: Hansson
authors: Amber Biosciences AB, Lund, Sweden.
authors: Morten
authors: M
authors: Krogh
authors: Amber Biosciences AB, Lund, Sweden.
authors: Mats
authors: M
authors: Jönsson
authors: Institute of Clinical Sciences, Department of Oncology, Lund University, Sweden. Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Denmark.
authors: Mef
authors: M
authors: Nilbert
authors: Department of Immunotechnology, Lund University, Lund, Sweden. peter.james@immun.lth.se.
authors: Peter
authors: P
authors: James
authors: Institute of Clinical Sciences, Department of Oncology, Lund University, Sweden.
authors: Ana
authors: A
authors: Carneiro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D003599:Cytoskeleton / Q000378:metabolism; D005121:Extremities / Q000473:pathology*; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D006801:Humans; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000473:pathology*; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D059505:Telomere Homeostasis; D035441:Thoracic Wall / Q000473:pathology*