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TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals

TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals
TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals
Background: fusion gene formation plays roles in both oncogenesis and evolution by facilitating the acquisition of novel functions. Here we describe the first example of a human polymorphic in-frame fusion of two unrelated genes associated with a copy number variant (CNV).
Design and methods: genomic array comparative hybridization (CGH) was used to identify cryptic oncogenic fusion genes. Fusion gene structure and origin was examined using molecular biological and computational methods. Phenotype associations were examined using PopGen cohorts.
Results: targeted array CGH to identify cryptic oncogenic fusion genes in patients with atypical myeloproliferative neoplasms identified a 111 kb amplification with breakpoints within TRK-fused gene (TFG, a target of translocations in lymphoma and thyroid tumors) and G-protein-coupled receptor 128 (GPR128) resulting in an expressed in-frame TFG-GPR128 fusion transcript. The fusion gene was also identified in healthy individuals at a frequency of 0.02 (3/120). Normally both genes are in identical orientations with TFG immediately downstream of GPR128. In individuals with a CNV amplification, one or two copies of the TFG-GPR128 fusion are found between the two parental genes. The breakpoints share a region of microhomology, and haplotype and microsatellite analysis indicate a single ancestral origin. Analysis of PopGen cohorts showed no obvious phenotype association. An in silico search of EST databases found no other CNV amplification-associated fusion transcripts, suggesting this is an uncommon event.
Conclusions: the finding of a polymorphic gene fusion in healthy individuals adds another layer to the complexity of human genome variation and emphasizes the importance of careful discrimination of oncogenic changes found in tumor samples from non-pathogenic normal variation
fusion gene, oncogenesis, targeted array, genomic array comparative hybridization
0390-6078
20-26
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Ernst, Thomas
96c7805b-c900-4545-9f93-1a83d789cb56
Fiebig, Andreas
16336973-f4fb-4fa7-af10-4f8e24e5f0b1
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Grand, Francis
c0b07bd4-8b60-4664-aaf7-0b8aefa0ef0f
Erben, Phillip
30ce462f-e220-4cce-a805-792cdbf27b0a
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Schreiber, Stefan
354f9219-7b03-447b-a651-9f5909cc8b9f
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Chase, Andrew
a40a09c2-3073-4655-ba0b-a802e34914b5
Ernst, Thomas
96c7805b-c900-4545-9f93-1a83d789cb56
Fiebig, Andreas
16336973-f4fb-4fa7-af10-4f8e24e5f0b1
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Grand, Francis
c0b07bd4-8b60-4664-aaf7-0b8aefa0ef0f
Erben, Phillip
30ce462f-e220-4cce-a805-792cdbf27b0a
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Schreiber, Stefan
354f9219-7b03-447b-a651-9f5909cc8b9f
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4

Chase, Andrew, Ernst, Thomas, Fiebig, Andreas, Collins, Andrew, Grand, Francis, Erben, Phillip, Reiter, Andreas, Schreiber, Stefan and Cross, Nicholas C.P. (2010) TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals. Haematologica, 95 (1), 20-26. (doi:10.3324/haematol.2009.011536).

Record type: Article

Abstract

Background: fusion gene formation plays roles in both oncogenesis and evolution by facilitating the acquisition of novel functions. Here we describe the first example of a human polymorphic in-frame fusion of two unrelated genes associated with a copy number variant (CNV).
Design and methods: genomic array comparative hybridization (CGH) was used to identify cryptic oncogenic fusion genes. Fusion gene structure and origin was examined using molecular biological and computational methods. Phenotype associations were examined using PopGen cohorts.
Results: targeted array CGH to identify cryptic oncogenic fusion genes in patients with atypical myeloproliferative neoplasms identified a 111 kb amplification with breakpoints within TRK-fused gene (TFG, a target of translocations in lymphoma and thyroid tumors) and G-protein-coupled receptor 128 (GPR128) resulting in an expressed in-frame TFG-GPR128 fusion transcript. The fusion gene was also identified in healthy individuals at a frequency of 0.02 (3/120). Normally both genes are in identical orientations with TFG immediately downstream of GPR128. In individuals with a CNV amplification, one or two copies of the TFG-GPR128 fusion are found between the two parental genes. The breakpoints share a region of microhomology, and haplotype and microsatellite analysis indicate a single ancestral origin. Analysis of PopGen cohorts showed no obvious phenotype association. An in silico search of EST databases found no other CNV amplification-associated fusion transcripts, suggesting this is an uncommon event.
Conclusions: the finding of a polymorphic gene fusion in healthy individuals adds another layer to the complexity of human genome variation and emphasizes the importance of careful discrimination of oncogenic changes found in tumor samples from non-pathogenic normal variation

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Published date: January 2010
Keywords: fusion gene, oncogenesis, targeted array, genomic array comparative hybridization

Identifiers

Local EPrints ID: 69520
URI: http://eprints.soton.ac.uk/id/eprint/69520
ISSN: 0390-6078
PURE UUID: bae8816c-5815-4262-9671-f9945f901db2
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 18 Nov 2009
Last modified: 10 Sep 2019 00:55

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Contributors

Author: Andrew Chase
Author: Thomas Ernst
Author: Andreas Fiebig
Author: Andrew Collins ORCID iD
Author: Francis Grand
Author: Phillip Erben
Author: Andreas Reiter
Author: Stefan Schreiber

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