BTG1.md
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# BTG1
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## Overview
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-BTG1 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus.
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+BTG1 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Mutations in the BTG1 gene have been implicated in the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL) through functional exploration in vivo. There is evidence that BTG1 mutations afford germinal center (GC) B cells with a fitness advantage relative to un-mutated counterparts.<sup>1</sup>
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## Relevance tier by entity
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|Entity|Tier|Description |
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|:------:|:----:|--------------------------------------|
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-|BL |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |
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|DLBCL |1-a | aSHM target and high-confidence DLBCL gene |
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|FL |1-a | aSHM target and high-confidence FL gene |
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+|BL |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |
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## Mutation incidence in large patient cohorts (GAMBL reanalysis)
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|Entity|source |frequency (%)|
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|:------:|:---------------------:|:-------------:|
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-|BL |GAMBL genomes+capture| 0.46 |
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-|BL |Thomas cohort | NA |
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-|BL |Panea cohort | NA |
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|DLBCL |GAMBL genomes |10.13 |
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|DLBCL |Schmitz cohort |14.47 |
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|DLBCL |Reddy cohort | 7.51 |
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|DLBCL |Chapuy cohort |14.53 |
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|FL |GAMBL genomes | 6.47 |
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+|BL |GAMBL genomes+capture| 0.46 |
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+|BL |Thomas cohort | 0 |
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+|BL |Panea cohort | 0 |
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## Mutation pattern and selective pressure estimates
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## BTG1 Hotspots
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+*Q36H* Conditional knock-in mouse models expressing the BTG1 Q36H mutation in B cells have shown that these mutations lead to earlier onset of lymphoma, shorter survival, and dysplastic B cell infiltration into non-lymphoid organs. These findings reinforce the role of BTG1 mutations in enhancing lymphoma aggressiveness.<sup>1</sup>
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| Chromosome |Coordinate (hg19) | ref>alt | HGVSp |
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| :---:| :---: | :--: | :---: |
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| chr12 | 92539221 | G>A | L31F |
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View all variants in GenomePaint [hg19](https://www.bcgsc.ca/downloads/morinlab/GAMBL/test/genes/BTG1.html) or [hg38](https://www.bcgsc.ca/downloads/morinlab/GAMBL/test/genes/BTG1_hg38.html)
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![image](images/proteinpaint/BTG1.svg)
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+## References
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+1. *Mlynarczyk C, Teater M, Pae J, Chin CR, Wang L, Arulraj T, Barisic D, Papin A, Hoehn KB, Kots E, Ersching J, Bandyopadhyay A, Barin E, Poh HX, Evans CM, Chadburn A, Chen Z, Shen H, Isles HM, Pelzer B, Tsialta I, Doane AS, Geng H, Rehman MH, Melnick J, Morgan W, Nguyen DTT, Elemento O, Kharas MG, Jaffrey SR, Scott DW, Khelashvili G, Meyer-Hermann M, Victora GD, Melnick A. BTG1 mutation yields supercompetitive B cells primed for malignant transformation. Science. 2023 Jan 20;379(6629):eabj7412. doi: 10.1126/science.abj7412. Epub 2023 Jan 20. PMID: 36656933; PMCID: PMC10515739.*
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