Molecular genetics of sarcomas: Applications to diagnoses and therapy

Junya Toguchida, Tomitaka Nakayama

    Research output: Contribution to journalReview article

    25 Scopus citations


    Sarcomas are mesenchymal cancers consisting of tumors with various clinical and pathological features. Some of them compel affected individuals to lose important musculoskeletal functions, and some of them are highly malignant and life-threatening. A great amount of genetic information for sarcomas has accumulated during the past two decades, contributing diagnoses and treatments. From the standpoint of molecular genetics, sarcomas are classified into two groups: those with defined genetic alterations and those with various genetic alterations. The genetic alterations in the first group include reciprocal translocations resulting in fusion oncoproteins and oncogenic mutations of defined genes such as those of the ckit gene in gastrointestinal stromal tumors. The function of fusion proteins includes transcription regulator, signal transducer, chromatic remodeling factor, and growth factor, some of which are suitable targets for the molecular therapy. In tumors belonging to the second group, the number of which is far larger than those of the first group, considerable genetic heterogeneity was found even among tumors with same pathological diagnosis. The disruption of the RB and p53 pathways was frequently found, resulting in the dysregulation of cell cycle and the genomic instability. The application of molecular target therapy for tumors in this group requires novel strategies to overcome cross talk between different signal pathways. Recent evidence from in vitro and in vivo experiments has indicated that the cells of origin of sarcomas are tissue stem cells such as mesenchymal stem cells, and the application of stem cell biology holds the promise of novel treatment options.

    Original languageEnglish (US)
    Pages (from-to)1573-1580
    Number of pages8
    JournalCancer science
    Issue number9
    StatePublished - Sep 1 2009

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Fingerprint Dive into the research topics of 'Molecular genetics of sarcomas: Applications to diagnoses and therapy'. Together they form a unique fingerprint.

  • Cite this