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Global Translational Medicine Fusion events identified in tumor

Figure 1. Timeline of fusion gene research.

[34]
found a minute chromosome replacing one of the four and the nucleus . Nucleoporin fusion consist of the
smallest autosomes of chronic granulocytic leukemia N-terminal FG-repeat intrinsically disordered regions
cultured from peripheral blood in 1962 . The aberrant of nucleoporin fused to DNA-binding factors . Also,
[35]
[20]
chromosomal rearrangement was then named as the activation of RNA polymerase II activates BRD4
“Philadelphia chromosome” to commemorate University and SWI/SNF pathway. Receptor tyrosine kinase (RTK)
of Philadelphia where they both work in. The fusion signaling is an essential process for conveying signals
protein encoded by BCR-ABL fusion is an abnormal from the marginal part to the inner part of cell . Fusion
[36]
tyrosine kinase that drives the development of myeloid genes between RTKs play an important role in tumor
leukemia; a drug was successfully developed against this differentiation and progression . The transcription
[37]
fusion protein for healing CML . Structure variants that of NPM-ALK fusion in anaplastic large-cell lymphoma
[28]
lead to tumorigenesis by kinase activation are found in produces mRNAs that are distinct from stress granules
less frequency in solid tumor than that in hematologic and are dependent on the activation of anaplastic
[38]
malignancies, due to the difficult sample collection and lymphoma kinase (ALK) fusion protein . In a similar
technological limitation. RET fused to neurotrophic way, the phosphorylation of the intracellular domain of
tyrosine kinase receptor type 1 (NTRK1) protein in thyroid the RTK activates the downstream signaling pathway to
cancer was the first fusion kinases found in solid tumors induce tumor malignancy. Multiple recent studies have
in 1985 . With the advancement of Sanger sequencing, reported that EML4-ALK (an RTK oncofusion) is fused
[29]
cytogenetic analysis and FISH, ETS variant 6 (ETV6) to the cytoplasmic domain of the ALK, undergoing phase
and NTRK3 fusion was identified in a rare subgroup separation of the cell cycle with downstream effectors to
of breast cancer, the secretory breast carcinoma . The form signaling-competent condensates in both lung cell
[30]
FET fusion gene was first reported in the early 1990s in lines and patient-derived xenograft [39,40] . Enrichment of
patients with malignant soft-tissue cancers, for example, protein binding counterparts of ALK, such as SOS1 and
Ewing’s sarcoma . The respective RNA-binding proteins growth factor receptor-bound protein 2, is necessary for
[31]
are fused to DNA-binding domains, forming ectopic forming punctuated fusion protein to enhance signaling
[41]
condensates on DNA . Overexpression of FET gene activity . Another RTK fusion gene, CCCD6-RET,
[32]
recruits the transcriptional machinery, including RNA demonstrates a kinase-independent fusion pattern that
polymerase II, thereby activating BRD4 and SWI/SNF the N-terminal coiled-coil domain of CCCD6 is sufficient
pathway . Nucleoporins belong to a multi-subunit to drive dimeric interactions. Inhibiting CCCD6-RET
[33]
complex that acts as a gateway between the cytoplasm leads to decreased downstream signaling, indicating

Volume 1 Issue 1 (2022) 3 https://doi.org/10.36922/gtm.v1i1.54