Proteomics of Bone and Soft Tissue Sarcomas

Sinclair      R. Dundas; Graeme      I. Murray

Abstract

Bone and soft tissue sarcomas are a diverse group of malignancies derived from mesenchymal tissue. Numerous different sub-types of sarcoma can be identified histologically and this reflects the capacity of mesenchymal precursor cells to differentiate along recognisable somatic lineages, although some sarcomas do not display any clear line of differentiation and form tumours with no obvious normal cellular counterpart. The morphological heterogeneity of sarcomas is paralleled by differences in biological behaviour that contribute to difficulties in understanding tumour progression and patterns of response to treatment. Although five-year survival rates of up to 80% can be achieved for localised sarcomas, some specific high-grade histological subtypes continue to portent poor prognosis, and metastasis at presentation remains a common problem. Identifying in advance the chemosensitivity of primary sarcomas, those sarcomas destined to metastasise, and successfully treating metastatic disease continues to pose a significant challenge.

Proteomic analysis combined with mass spectroscopy and bioinformatics is a powerful approach to analysing molecular abnormalities responsible for the biological behaviour of sarcomas. Investigating abnormalities downstream of the genome using protein expression analysis has several important advantages over DNA sequencing or mRNA expression studies in cancer research. Sophisticated proteomic technologies have only recently been applied to the study of sarcomas with the principle aim of discovering new disease-specific biomarkers that will facilitate more accurate classification of sarcomas into clinically relevant sub-types as well as identifying novel therapeutic targets. This article will review recent developments and summarise the emerging role of proteomic analysis in the strategy of applying molecular classification to both the diagnosis and targeted treatment of sarcomas.

Keywords: biomarkers, bone sarcoma, molecular diagnosis, proteomics, soft tissue sarcoma, electrophoresis, Two dimensional difference gel, Two dimensional polyacrylamide gel electrophoresis, Crystalline a/b, Ewing’s sarcoma, Ezrin, Fluorescence in situ hybridisation, Gastrointestinal stromal tumour, "Matrix-assisted laser desorption ionisation mass spectroscopy", Mass spectrometry, Mammalian target of rapamycin, Polymerase chain reaction, Post-translational modifications, Surface-enhanced laser desorption ionisation, Time-of-flight