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Gene & Protein in Disease Gene fusions and chimeric RNAs

Advancements in technologies such as high-throughput SEPT7P2 and exon 4 from PSPH, separated by 10.2 Mb.
data analysis, deep sequencing, and accurate bioinformatic Septin 7 pseudogene 2 (SEPT7P2) is a pseudogene similar
tools will further aid in the identification of new chimeric to SEPT7, expressed across various tissues and involved in
RNAs in thyroid cancer. multiple biological processes. Phosphoserine phosphatase
(PSPH) is a protein-coding gene, and its abnormal
3.5. Chimeric RNAs in different cancers expression has been linked to several carcinomas. Further
With advancements in technology, various experimental investigation revealed that suppressing the SEPT7P2–
techniques, including RNA sequencing, whole-genome PSPH fusion transcript could enhance cell growth and
sequencing, and bioinformatic software tools, have cancer cell spread, likely due to the increased expression
significantly contributed to the identification and of PSPH. 73
confirmation of gene fusions across numerous cancer Furthermore, Wu et al. (2018) reported the presence of
types. These findings have been deposited in various a chimeric RNA, LHX6–NDUFA8, in both cervical cancer
databases. A study conducted by Tao et al. (2018) identified tissue and pap smear specimens. This chimeric RNA has
a recurring chimeric RNA, COL7A1–UCN2, in human two isoforms: LHX6–NDUFA8-e8e2 and LHX6–NDUFA8-
laryngeal cancer, which was formed through alternative e8e3, both showing significant prevalence in cervical
splicing. Both genes are located on chromosome 3, with cancer. To evaluate the potential of fusion RNAs for
the COL7A1 fusion occurring at exons 113 – 117 and the inclusion in pap smear screenings for cervical cancer and
junction with UCN2 at exon 2. The authors reported that cervical intraepithelial neoplasia, the researchers analyzed
laryngeal cancer patients positive for the COL7A1–UCN2 the expression of both isoforms in pap smear samples.
fusion had significantly poorer overall survival than those The findings showed a favorable detection rate for both
negative for the fusion. In addition, COL7A1 mRNA isoforms, correlating with the presence of cervical cancer.
expression was reduced in malignant tissues, whereas the Both isoforms of LHX6–NDUFA8 result from cis-splicing
formation of COL7A1–UCN2 chimeric RNA bypassed the events between neighboring genes, a process known as cis-
tumor-suppressing effects of TGF-β1, facilitating tumor SAGe. Gene fusions detected in various cancer types are
74
invasion and growth. 72 listed in Table 1.
Similarly, Wang et al. (2019) identified a SEPT7P2– 4. Chimeric RNAs in healthy tissues and
PSPH chimeric transcript in nasopharyngeal carcinoma, cells
which was formed through trans-splicing between adjacent
genes. Both genes are located on chromosome 7, with the Previously, chimeric RNAs were thought to be associated
chimeric transcript resulting from the fusion of exon 1 from solely with tumorigenesis. However, advancements in

Table 1. Gene fusions in various cancer types

Cancer type Gene fusion Role in cancer References
Prostate cancer SLC45A3–ELK4 Regulates cell proliferation 77, 78
Prostate cancer TMPRSS2–ERG Oncogenic pathway activation 79
Prostate cancer KLK4–KLKP1 Impacts cell proliferation 80
Prostate cancer UNC5D–NRG1 Predicted protein-coding fusion 81
Esophageal cancer GOLM1–NAA35 Tumor growth and progression 82
Esophageal cancer ASTN2–PAPPAas Enhances cell migration 83
Lung cancer KIF5B–MET Oncogenic properties 84
Lung cancer SOS1–ALK Metastatic lung adenocarcinoma 85
Lung cancer CLIP1–LTK Oncogenic driver in NSCLC 86
Thyroid cancer STRN–ALK Activates MAPK signaling pathway 87
Thyroid cancer ANKRD26–RET Continuous activation of tyrosine kinase 8
Thyroid cancer TFG–RET Oncogenic transformation 89
Laryngeal cancer COL7A1–UCN2 Facilitates tumor invasion and growth 90
Nasopharyngeal cancer SEPT7P2–PSPH Promotes cell proliferation 91
cervical Cancer LHX6–NDUFA8 Prevalence in cervical cancer 92

Volume 4 Issue 1 (2025) 8 doi: 10.36922/gpd.3641