BTG1 - morinlab/LLMPP GitHub Wiki


bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @morinFrequentMutationHistonemodifying2011, @delageBTG1InactivationDrives2023, @burkhardtClinicalRelevanceMolecular2022, @sarkozyMutationalLandscapeGray2021, @mlynarczykBTG1MutationYields2023,

TOC

Overview

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.

Experimental Evidence

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.[@delageBTG1InactivationDrives2023] Another study demonstrated that specific BTG1 mutations afford germinal center (GC) B cells with a fitness advantage relative to un-mutated counterparts.[@mlynarczykBTG1MutationYields2023]

Relevance tier by entity

include:tables/table1_BTG1.md

Mutation incidence in large patient cohorts (GAMBL reanalysis)

DLBCL

include:tables/DLBCL_BTG1.md

FL

include:tables/FL_BTG1.md

BL

include:tables/BL_BTG1.md

Mutation pattern and selective pressure estimates

include:tables/dnds_BTG1.md

aSHM regions

chr_name hg19_start hg19_end region regulatory_comment
chr12 92537999 92539598 TSS active_promoter

BTG1 Hotspots

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.[@sarkozyMutationalLandscapeGray2021]

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.[@mlynarczykBTG1MutationYields2023]

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

include:tables/browser_BTG1.md

Expression

include:tables/mermaid_BTG1.md

References