Advances in sarcoma genomics and new therapeutic targets View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-07-14

AUTHORS

Barry S. Taylor, Jordi Barretina, Robert G. Maki, Cristina R. Antonescu, Samuel Singer, Marc Ladanyi

ABSTRACT

Key PointsHuman sarcomas are uncommon malignancies that arise from mesenchymal cell types, have varied genetic origins and are clinically heterogeneous. Many sarcomas arise de novo, driven by a single genetic abnormality, and some are progressive and harbour complex genomes.Three core and context-dependent molecular mechanisms drive sarcomagenesis: dysregulation of gene expression by aberrant, chimeric transcription factors generated by specific gene fusions in translocation-associated sarcomas, somatic mutations affecting key signalling pathways and DNA copy-number abnormalities.Novel genomic findings from diverse approaches in sarcoma are identifying point mutations that co-occur with translocations, lineage-specific oncogenes, chromosome remodelling events, and both genomic alterations and mutations that alter canonical signalling and differentiation pathways.As integrative genomics and massively parallel sequencing increase the pace of discovery for the most common lesions in all but the rarest sarcomas, this necessitates renewed focus on developing in vitro and in vivo sarcoma models for accompanying target discovery and functional annotation of sarcoma genomes with genomics-guided functional genetics.Although conventional modalities predominate in sarcoma treatment, new approaches to target aberrant signalling with specific therapies, overcome acquired resistance and target unconventional pathways are rapidly evolving. More... »

PAGES

541-557

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    DOI

    http://dx.doi.org/10.1038/nrc3087

    DIMENSIONS

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    PUBMED

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