Translocation-Related Sarcomas
Posted: Thu Nov 18, 2021 8:43 am
Translocation-Related
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: Soft tissue sarcoma, chromosomal translocation, translocation-related sarcoma, Ewing sarcoma breakpoint region 1, forkhead box transcription factor O, transcription factor E3, anaplastic lymphoma kinase, neurotrophic tyrosine kinase
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320865/
https://pubmed.ncbi.nlm.nih.gov/27979841/
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: Soft tissue sarcoma, chromosomal translocation, translocation-related sarcoma, Ewing sarcoma breakpoint region 1, forkhead box transcription factor O, transcription factor E3, anaplastic lymphoma kinase, neurotrophic tyrosine kinase
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320865/
“Modeling Alveolar Soft Part Sarcoma Unveils Novel Mechanisms of Metastasis“A rare subtype of STS is alveolar soft part sarcoma (ASPS), which accounts for <1% of all STS and occurs mostly at adolescent and young adult (AYA) ages [7]. An unbalanced chromosomal translocation, t(X;17)(p11;q25), is characteristic of ASPS, and it is also found in pediatric papillary renal cell cancers [60,61]. The translocation t(X;17)(p11;q25) includes the fusion of ASPL-TFE3, which brings the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of ASPS [62]. The detection of TFE3 by immunohistochemistry is useful for the pathological diagnosis of ASPS [63].
https://pubmed.ncbi.nlm.nih.gov/27979841/