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.

Relevance tier by entity

Entity	Tier	Description
DLBCL	1	high-confidence DLBCL gene
FL	1	high-confidence FL gene

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

References

1. 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.
2. 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.