TNFAIP3 and neoplasm: However, secondary resistance is almost inevitable, and tumours with oncogenic NF-κB-pathway alterations affecting signalling events downstream of BTK, such CARD11 mutations and A20 mutations and deletions, are naturally refractory to this agent, thereby limiting its clinical utility, especially in patients with aggressive NF-κB-pathway mutated lymphomas (Table 1) [113].