Figure 4.

Recurrent gain-of-function mutations affecting signaling pathways in lymphoma. (a) Activating mutations in the CARD11 coiled-coil (CC) domain. Shown are frequencies of mutations affecting amino acids within the CC domain in DLBCL, gastric lymphoma, and primary central nervous system lymphoma, summarized from References 52, 53, 263, 278, 368. (b) Mutations in the B cell receptor (BCR) subunit CD79B in ABC DLBCL. Shown are mutations affecting the first tyrosine of the CD79B immunoreceptor tyrosine-based activation motif (ITAM) signaling module. These mutations are present in 18% of ABC DLBCL tumors, but other mutations or deletions in the CD79B or CD79A ITAM region occur in an additional 3% of cases (not shown) (106). (c) Location of MYD88 mutations acquired by human lymphomas. Shown is the NMR structure of the MYD88 Toll/interleukin-1 receptor (TIR) domain, with the amino acids that are mutated in lymphoma indicated by their side chains (39). The most prevalent mutation, L265P (arrow), is located in the hydrophobic core of this domain. Several other recurrent mutants reside in the B-B loop that is involved in interactions with other TIR domains present in Toll-like receptors (TLRs). See text for details.