Translocation-Related Sarcomas

Abstract

Chromosomal translocations are observed in approximately 20% of soft tissue sarcomas (STS). With the advances in pathological examination technology, the identification of translocations has enabled precise diagnoses and classifications of STS, and it has been suggested that the presence of and differences in translocations could be prognostic factors in some translocation-related sarcomas. Most of the translocations in STS were not regarded as targets of molecular therapies until recently. However, trabectedin, an alkylating agent, has shown clinical benefits against translocation-related sarcoma based on a modulation of the transcription of the tumor's oncogenic fusion proteins. Many molecular-targeted drugs that are specific to translocations (e.g., anaplastic lymphoma kinase and tropomyosin kinase related fusion proteins) have emerged. The progress in gene technologies has allowed researchers to identify and even induce new translocations and fusion proteins, which might become targets of molecular-targeted therapies. In this review, we discuss the clinical significance of translocation-related sarcomas, including their diagnoses and targeted therapies.

Keywords: Ewing sarcoma breakpoint region 1; Soft tissue sarcoma; anaplastic lymphoma kinase; chromosomal translocation; forkhead box transcription factor O; neurotrophic tyrosine kinase; transcription factor E3; translocation-related sarcoma.

Figure 1

Chromosomal translocations in STS and their locations. Abbreviations: ALK; anaplastic lymphoma kinase, DUX4; double-homeobox, FOXO; forkhead box transcription factor O, NTRK; neurotrophic tyrosine kinase, TFE3; transcription factor E3.