Fusion gene

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A fusion gene is a hybrid gene formed from two previously separate genes. It can occur as a result of: translocation, interstitial deletion, or chromosomal inversion.

A schematic showing the ways a fusion gene can occur at a chromosomal level.

Oncogenes[edit]

Often, fusion genes are oncogenes that cause cancer; these include BCR-ABL,[1] 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.[2] Most fusion genes are found from hematological cancers, sarcomas, and prostate cancer.[3][4]

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.[5] Oncogenic fusion transcripts may also be caused by trans-splicing or read-through events.[6]

Diagnostics[edit]

Presence of certain chromosomal aberrations and their resulting fusion genes is commonly used within cancer diagnostics in order to set a precise diagnosis. Chromosome banding analysis, fluorescence In Situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR) are common methods employed at diagnostic laboratories. These methods all have their distinct shortcomings due to the very complex nature of cancer genomes. Recent developments such as high-throughput sequencing[7] and custom DNA microarrays bear promise of introduction of more efficient methods.[8]

Research applications[edit]

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.[9] The protein synthesized when a fusion gene is expressed is called a fusion protein.

See also[edit]

References[edit]

  1. ^ Nowell, PC; Hungerford, DA (1960). "A minute chromosome in chronic granulocytic leukemia" (PDF). Science 132 (3438): 1488–1501 [1497]. doi:10.1126/science.132.3438.1488. 
  2. ^ Tomlins, SA; Rhodes, DR; Perner, S; Dhanasekaran, SM; Mehra, R; Sun, XW; Varambally, S; Cao, X et al. (2005). "Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer". Science 310 (5748): 644–8. doi:10.1126/science.1117679. PMID 16254181. 
  3. ^ Mitelman, F; Johansson, B; Mertens, F (2007). "The impact of translocations and gene fusions on cancer causation". Nature reviews. Cancer 7 (4): 233–45. doi:10.1038/nrc2091. PMID 17361217. 
  4. ^ Teixeira, MR (2006). "Recurrent fusion oncogenes in carcinomas". Critical reviews in oncogenesis 12 (3–4): 257–71. PMID 17425505. 
  5. ^ Vega, F; Medeiros, LJ (2003). "Chromosomal translocations involved in non-Hodgkin lymphomas". Archives of pathology & laboratory medicine 127 (9): 1148–60. doi:10.1043/1543-2165(2003)127<1148:CTIINL>2.0.CO;2 (inactive 2014-03-23). PMID 12946230. 
  6. ^ Nacu, S; Yuan, W; Kan, Z; Bhatt, D; Rivers, CS; Stinson, J; Peters, BA; Modrusan, Z; Jung, K; Seshagiri, Somasekar; Wu, Thomas D (2011). "Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples". BMC Med Genomics 4 (1): 11. doi:10.1186/1755-8794-4-11. PMC 3041646. PMID 21261984. 
  7. ^ Maher, CA; Kumar-Sinha, C; Cao, X; Kalyana-Sundaram, S; Han, B; Jing, X; Sam, L; Barrette, T et al. (2009). "Transcriptome Sequencing to Detect Gene Fusions in Cancer". Nature 458 (7234): 97–101. doi:10.1038/nature07638. PMC 2725402. PMID 19136943. 
  8. ^ Skotheim, RI; Thomassen, GO; Eken, M; Lind, GE; Micci, F; Ribeiro, FR; Cerveira, N; Teixeira, MR; Heim, S; Rognes, Torbjørn; Lothe, Ragnhild A (2009). "A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis". Molecular cancer 8: 5. doi:10.1186/1476-4598-8-5. PMC 2633275. PMID 19152679. 
  9. ^ Prendergast, FG; Mann, KG (1978). "Chemical and physical properties of aequorin and the green fluorescent protein isolated from Aequorea forskålea". Biochemistry 17 (17): 3448–53. doi:10.1021/bi00610a004. PMID 28749.