Fusion gene
Encyclopedia
A fusion gene is a hybrid gene formed from two previously separate genes. It can occur as the result of a translocation
, interstitial deletion, or chromosomal inversion
. Often, fusion genes are oncogene
s; examples include BCR-ABL
, TEL-AML1 (ALL
with t(12 ; 21)), AML1-ETO (M2 AML with t(8 ; 21)) and TMPRSS2
-ERG
with an interstitial deletion on chromosome 21, often occurring in prostate cancer. Most fusion genes are found from hematological cancers, sarcomas and prostate cancer.
Oncogenic fusion genes may lead to a gene product with a new or different function from the two fusion partners. Alternatively, a proto-oncogene is fused to a strong promoter, and thereby the oncogenic function is set to function by an upregulation caused by the strong promoter of the upstream fusion partner. The latter is common in lymphomas, where oncogenes are juxtaposed to the promoters of the immunoglobulin genes. Oncogenic fusion transcript
s may also be caused by trans-splicing
or read-through events .
Presence of certain chromosomal aberrations and their resulting fusion genes is commonly used within cancer diagnostics in order to set a precise diagnosis. In routine diagnostic laboratories the following methods are most commonly used: chromosome banding analysis, fluorescence in situ hybridisation, and RT-PCR. These methods all have their distinct shortcomings due to the very complex nature of cancer genomes. Recent developments such as high-throughput sequencing
and custom-designed DNA microarray
s bear promise of introduction of more efficient methods.
Biologists may also deliberately create fusion genes for research purposes. For example, by creating a fusion gene of a protein of interest and green fluorescent protein
, the protein of interest may be observed in cells
or tissue
using fluorescence microscopy
. The protein synthesized when a fusion gene is expressed
is called a fusion protein
.
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
, interstitial deletion, or chromosomal inversion
Chromosomal inversion
An inversion is a chromosome rearrangement in which a segment of a chromosome is reversed end to end. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself. Inversions are of two types: paracentric and pericentric.Paracentric inversions do not include the...
. Often, fusion genes are oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
s; examples include BCR-ABL
Philadelphia chromosome
Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
, TEL-AML1 (ALL
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone...
with t(12 ; 21)), AML1-ETO (M2 AML with t(8 ; 21)) and TMPRSS2
TMPRSS2
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene.-ERG Gene Fusion:TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1 through gene fusion. TMPRSS2-ERG fusion gene is the most...
-ERG
ERG (gene)
Transcriptional regulator ERG is a protein that in humans is encoded by the ERG gene . ERG is a member of the ETS family of transcription factors.- Function :...
with an interstitial deletion on chromosome 21, often occurring in prostate cancer. Most fusion genes are found from hematological cancers, sarcomas and prostate cancer.
Oncogenic fusion genes may lead to a gene product with a new or different function from the two fusion partners. Alternatively, a proto-oncogene is fused to a strong promoter, and thereby the oncogenic function is set to function by an upregulation caused by the strong promoter of the upstream fusion partner. The latter is common in lymphomas, where oncogenes are juxtaposed to the promoters of the immunoglobulin genes. Oncogenic fusion transcript
Fusion transcript
Fusion transcript is a chimeric RNA encoded by a fusion gene or by two different genes by subsequent trans-splicing. Certain fusion transcripts are commonly produced by cancer cells, and detection of fusion transcripts is part of routine diagnostics of certain cancer types....
s may also be caused by trans-splicing
Trans-splicing
Trans-splicing is a special form of RNA processing in eukaryotes where exons from two different primary RNA transcripts are joined end to end and ligated....
or read-through events .
Presence of certain chromosomal aberrations and their resulting fusion genes is commonly used within cancer diagnostics in order to set a precise diagnosis. In routine diagnostic laboratories the following methods are most commonly used: chromosome banding analysis, fluorescence in situ hybridisation, and RT-PCR. These methods all have their distinct shortcomings due to the very complex nature of cancer genomes. Recent developments such as high-throughput sequencing
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
and custom-designed DNA microarray
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
s bear promise of introduction of more efficient methods.
Biologists may also deliberately create fusion genes for research purposes. For example, by creating a fusion gene of a protein of interest and green fluorescent protein
Green fluorescent protein
The green fluorescent protein is a protein composed of 238 amino acid residues that exhibits bright green fluorescence when exposed to blue light. Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the...
, the protein of interest may be observed in cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
or tissue
Biological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
using fluorescence microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
. The protein synthesized when a fusion gene is expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
is called a fusion protein
Fusion protein
Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...
.