BTK - morinlab/LLMPP GitHub Wiki

bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true

BTK

One study reported BTK mutations in approximately 7% of FL and 11% of transformed FL cases.1 Another showed these mutations were more common, and typically co-occur in tumours with BCL2 translocations. Despite the known role of certain BTK mutations in acquired resistance to BTK inhibitors, these mutations were found in BTK inhibitor-naïve patients.2 These mutations often occur in treatment-naive patients and lead to inactivation of the BTK protein through destabilization or by altering key residues involved in enzymatic activity.1 The mutation pattern in DLBCL and FL implies the preferential accumulation of inactivating mutations. No notable hot spots have been described in this gene in the context of the cancers listed below.

History

%%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%%
timeline
    title Publication timing
      2017-01-26 : Krysiak : FL
      2017-05-01 : Albuquerque : DLBCL
      2017-10-10 : Reddy : DLBCL
Loading

Relevance tier by entity

Entity Tier Description
DLBCL 1 high-confidence DLBCL gene[@albuquerqueEnhancingKnowledgeDiscovery2017a; @reddyGeneticFunctionalDrivers2017]
FL 1 high-confidence FL gene [@krysiakRecurrentSomaticMutations2017b]

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity source frequency (%)
DLBCL GAMBL genomes 6.88
DLBCL Schmitz cohort 3.40
DLBCL Reddy cohort 3.10
DLBCL Chapuy cohort 2.14
FL GAMBL genomes 6.93

Mutation pattern and selective pressure estimates

Entity aSHM Significant selection dN/dS (missense) dN/dS (nonsense)
BL No No 0.964 8.202
DLBCL No Yes 18.082 28.027
FL No Yes 39.808 35.548

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

BTK Expression

References

  1. Krysiak K, Gomez F, White BS, Matlock M, Miller CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR, Berrien-Elliott MM, Bartlett NL, Griffith M, Griffith OL, Fehniger TA. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017 Jan 26;129(4):473–483. PMCID: PMC5270390

  2. Albuquerque MA, Grande BM, Ritch EJ, Pararajalingam P, Jessa S, Krzywinski M, Grewal JK, Shah SP, Boutros PC, Morin RD. Enhancing knowledge discovery from cancer genomics data with Galaxy. Gigascience. 2017 May 1;6(5):1–13. PMCID: PMC5437943

  3. Hu N, Wang F, Sun T, Xu Z, Zhang J, Bernard D, Xu S, Wang S, Kaminski M, Devata S, Phillips T, Malek SN. Follicular Lymphoma-associated BTK Mutations are Inactivating Resulting in Augmented AKT Activation. Clin Cancer Res. 2021 Apr 15;27(8):2301-2313. doi: 10.1158/1078-0432.CCR-20-3741. Epub 2021 Jan 8. PMID: 33419778; PMCID: PMC8046715.

  4. Schejbel L, Breinholt MF, Gang AO, Nielsen TH, Pedersen LM, Høgdall E, Nørgaard P. Inactivating BTK mutations in large B-cell lymphoma in a real-world cohort: Strong correlation with BCL2 translocation. EJHaem. 2022 Jun 24;3(3):936-939. doi: 10.1002/jha2.489. PMID: 36051027; PMCID: PMC9421985.

⚠️ **GitHub.com Fallback** ⚠️