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What is gene fusion?

A fusion gene occurs when all or part of the sequences of two genes fuse to form a new gene. This can occur as a result of a chromosomal translocation, interstitial deletion, or chromosomal inversion.
 
 
 

Mechanisms of Generation

There are three common mechanisms for gene fusion:
1) Chromosomal translocation. As shown in Figure A above, two segments on chromosomes 1 and 2 cross over, resulting in the fusion of the light green gene on chromosome 1 with the orange gene on chromosome 2.

2) Interstitial deletion. As shown in the figure above, a deletion occurs between the orange and light green genes on chromosome 3, ultimately leading to the fusion of the two genes.

3) Chromosomal inversion. For example, an inversion occurs between the orange and dark green genes on chromosome 4, ultimately leading to the fusion of the orange and light green genes.
 
Image source:Wikipedia
 

Why research Fusions?

Past research has consistently shown that gene fusions are closely associated with the development and progression of various diseases, particularly cancer, and can even be a direct cause of some cancers. Therefore, gene fusions have become a key area of research in current omics big data analysis.

Currently, many cancers have been reported to be closely associated with gene fusions, as shown in the following table:
 
Table 1. Number of gene fusion involver in major neoplasia subtypes
 
FDA-approved drugs targeting gene fusions in malignant disorders (Image source: Mertens et al. Nature Reviews Cancer, 2015)
 

Fusion Development Approach

If the desired site cannot be found in the natural sample, we can use cell engineering technology to edit specific chromosomal locations. The edited cell line has clear breakpoints and is completely identical to the natural sequence, enabling stable detection at the RNA level and testing the sensitivity, specificity, and stability of fusion gene detection.
 
The process is as follows:
1. Cell Engineering: In vitro synthesis of the fusion gene fragment and transfer into a natural cell sample to generate cells containing the fusion variant;

2. Amplification: Cell culture and passage amplification;

3. Extraction: RNA is extracted from the amplified cells;

4. Validation: Quality control verification is performed using Sanger sequencing and digital PCR. If fusion %AF or copy number testing is required, we also perform dPCR verification.
 
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 PCR Kits:PCR、Q-PCR、AMAS-PCR、DdPCR、Nested PCR......
 NGS Kits:WES、WGS、Panel
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