BTK
Overview
BTK (Bruton Tyrosine Kinase) is a non-receptor tyrosine kinase essential for B-cell receptor (BCR) signaling, survival, and differentiation. In B-cell malignancies, BTK propagates downstream NF-kappaB activation, and is therapeutically targeted by ibrutinib and next-generation covalent and non-covalent inhibitors. In DLBCL, BTK mutations contribute to constitutive BCR/NF-kappaB pathway activation, particularly in the ABC subtype.
Alterations observed in the corpus
- BTK was identified as a driver-gene cluster member in DLBCL within the B-cell-development and signaling functional group, based on whole-exome sequencing of 1001 de novo DLBCL patients. PMID:28985567
Cancer types (linked)
- DLBCLNOS: BTK mutations are included in the 150 recurrent driver genes identified in DLBCL. BTK is pharmacologically targetable; 36% of DLBCL patients harbor alterations in the 9 CRISPR-validated essential drivers that are direct targets of approved or trial-stage drugs, and BTK inhibitors are among the most clinically relevant agents for B-cell lymphomas. PMID:28985567
Co-occurrence and mutual exclusivity
- BTK clusters with other B-cell-development and NF-kappaB signaling drivers (CARD11, MYD88, IKBKB) that show ABC-selective CRISPR essentiality in DLBCL. PMID:28985567
Therapeutic relevance
- BTK is a direct target of ibrutinib and next-generation BTK inhibitors, which are approved or in trials for ABC DLBCL and other B-cell malignancies. The CRISPR screen in this cohort validated additional functional dependencies that complement BTK inhibition targets. PMID:28985567
Open questions
- CRISPR knockout data for BTK specifically was not separately reported in this study; its essentiality in established DLBCL cell lines relative to ABC- vs GCB-selective hits (CARD11, MYD88) remains to be clarified. PMID:28985567
Sources
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