Discovery, validation, and specificity assessment of NOTCH2 mutations in SMZL and other B cell lymphomas. A summary of the experimental design and results illustrates initial NOTCH2 mutation discovery in three of six index SMZL cases through WGS, all of which were confirmed as somatic mutations by traditional Sanger sequencing. Sanger sequencing of the C-terminal of NOTCH2 comprising exons 25–34 was performed in 93 additional SMZL cases comprising the validation cohort to establish the rate of recurrence of NOTCH2 mutations in SMZL. In total, 22 additional SMZL cases harbored mutations in the HD and PEST domains of NOTCH2. To assess the specificity of NOTCH2 mutations among other abnormal B cell proliferations, Sanger sequencing of NOTCH2 regions with recurrent mutations identified in discovery and validation samples of SMZL (exons 26, 27 and 34) was performed for 19 cases of nonsplenic marginal zone lymphoma (MALT-L), 14 cases of RLH, 15 chronic lymphocytic lymphoma (CLL/SLL), 44 low-grade follicular cell lymphoma (grade 1–2; FL), 15 HCL, and 15 MCL. To assess the consequences of NOTCH2 mutation on disease characteristics, clinical data were collected on a total of 46–53 SMZL cases including 11–12 cases with NOTCH2 mutation.