BTG1 - morinlab/LLMPP GitHub Wiki
BTG1 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. These mutations are a feature of the MCD genetic subgroup of DLBCL.
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. Knock-out of BTG1 did not lead to spontaneous lymphomagenesis but enhanced the lymphoproliferation induced by VavP-BCL2 and promoted lymphoma dissemination in xenotransplantation experiments.[@delageBTG1InactivationDrives2023a] Another study demonstrated that specific BTG1 mutations afford germinal center (GC) B cells with a fitness advantage relative to un-mutated counterparts.[@mlynarczykBTG1MutationYields2023b]
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timeline
title Publication timing
2011-07-27 : Morin : DLBCL
2012-03-06 : Lohr : DLBCL
2013-01-01 : Zhang : DLBCL
2013-08-15 : Morin : DLBCL
2017-10-10 : Reddy : DLBCL
2018-04-12 : Schmitz : DLBCL
2018-05-01 : Chapuy : DLBCL
2021-04-01 : Sarkozy : PMBL
2022-07-06 : Burkhardt : BL
| Entity | Tier | Description |
|---|---|---|
 |
1 | high-confidence MZL gene |
 |
1 | high-confidence PMBL/cHL/GZL gene[@sarkozyMutationalLandscapeGray2021a] |
 |
1-EE[@mlynarczykBTG1MutationYields2023b; @delageBTG1InactivationDrives2023a] | aSHM target and high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011] |
 |
1 | aSHM target and high-confidence FL gene |
 |
2 | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@burkhardtClinicalRelevanceMolecular2022b] |
| Entity | source | frequency (%) |
|---|---|---|
| DLBCL | GAMBL genomes | 10.13 |
| DLBCL | Schmitz cohort | 14.47 |
| DLBCL | Reddy cohort | 7.51 |
| DLBCL | Chapuy cohort | 14.53 |
| FL | GAMBL genomes | 6.47 |
| BL | GAMBL genomes+capture | 0.46 |
| BL | Thomas cohort | 0 |
| BL | Panea cohort | 0 |
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| BL | Yes | No | 0.000 | 0.000 |
| DLBCL | Yes | No | 0.498 | 1.085 |
| FL | Yes | No | 4.407 | 6.147 |
| chr_name | hg19_start | hg19_end | region | regulatory_comment |
|---|---|---|---|---|
| chr12 | 92537999 | 92539598 | TSS | active_promoter |
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.3
L26P, G66D, and I115V Have each been shown to be unable to rescue wild-type BTG1 activity in a xenotransplantation model, suggesting that they impair BTG1 function.2
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr12 | 92539221 | G>A | L31F |
| chr12 | 92539209 | G>A | R35* |
| chr12 | 92539204 | C>G | Q36H |
| chr12 | 92539203 | G>T | L37M |
| chr12 | 92539203 | G>C | L37V |
| chr12 | 92539198 | C>A | Q38H |
| chr12 | 92539195 | GG>CA | T39M |
| chr12 | 92539190 | C>T | S41N |
| chr12 | 92539189 | G>C | S41R |
| chr12 | 92539184 | C>T | S43N |
| chr12 | 92539179 | G>A | Q45* |
| chr12 | 92539174 | C>G | E46D |
| chr12 | 92539173 | G>C | L47V |
| chr12 | 92539167 | C>T | A49T |
| chr12 | 92539164 | C>T | E50K |
| chr12 | 92539164 | C>G | E50Q |
| chr12 | 92538218 | A>C | Y52D |
| chr12 | 92538217 | T>C | Y52C |
| chr12 | 92538215 | T>C | K53E |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
