Recurrent mutations and their relationship to disease progression in PCNSL. (A) Oncoprint of recurrent mutations and prognostically relevant copy number aberrations in 78 patients with newly diagnosed PCNSL treated with high-dose methotrexate plus rituximab–based induction (76 received MTR). Overall, 35 patients have progressed, 17 within the first 6 months. Frequent mutations involved MYD88 (80% patients, 82% of which were the L265P mutation), CD79B (38%), ETV6 (28%), BTG1 (28%), KMT2D (27%), PRDM1 (22%), CARD11 (17%), DUSP2 (14%), TP53 (10%), GNA13 (10%), BCL2 (8%), IRF4 (8%), CXCR4 (6%), and CD79A (6%). Fourteen patients (18%) had chromosome 6p CN-LOH and 2 had focal HD involving 6p21.3. (B). Frequency of genomic aberrations with respect to disease progression. The y-axis represents the percentage of a mutation in the progressed patients (n = 35) and nonprogressed patients (n = 43). Common aberrations associated with disease progression: 6p CN-LOH/6p21.3 HD (3.7-fold higher in progressors, P = .010, Fisher’s exact test); ETV6 mutations (1.8-fold higher in progressors); BTG1 mutations (1.8-fold higher in progressors); and TP53 mutations (3.7-fold higher in progressors). The combination of aberrations at these 4 loci (6p CN-LOH/6p21.3 HD, BTG1, ETV6, and TP53) was 2.2-fold higher in the progressors than the nonprogressors (p = 4e−6, Fisher’s exact test). Less frequent mutations involving IRF4, BCL2, and CD79A were also associated with progression (fold >2); however, these mutations occurred exclusively in patients with 6p CN-LOH/6p21.3 HD, or mutations involving BTG1, ETV6, or TP53. Mutations involving MYD88, CD79B, CARD11, KMT2D, and PRDM1 were frequent but did not correlate with progression (fold between 0.8 to 1.1). ABC, activated B cell; GCB, germinal center B cell; NA, not available.