SOCS1 Mutation Subtypes Predict Divergent Outcomes in DLBCL Patients

Abstract 419 Suppressor of cytokine signaling 1 ( SOCS1 ) is frequently mutated in Hodgkin, primary mediastinal and diffuse large B-cell lymphomas (DLBCL). In the primary mediastinal B-cell lymphoma line MedB-1, mutated SOCS1 abnormally stabilizes phospho-JAK2, thereby enhances STAT signaling leading to continuous proliferation. Here, we evaluated the prognostic value of SOCS1 mutations by full-length gene sequencing of SOCS1 in 154 comprehensively characterized DLBCL cases. By sequence analysis, we identified 90 SOCS1 mutations in 16% of lymphomas. We defined two distinct subtypes with respect to putative mutational consequences: those predicting the full-length ( minor ) and a truncated protein ( major ), respectively. Neither the SOCS1 mutation group, nor minor / major subgroups can be distinguished by clinical phenotype; however, assignment of four established expression-based classifiers revealed significant associations of SOCS1 major cases with germinal center - and specific pathway activation pattern signatures. Above all, SOCS1 major cases had an excellent overall survival, even better than the GCB-like subgroup (see Figure). SOCS1 minor cases had a dismal survival, even worse than the ABC gene signature group (see Figure). SOCS1 mutation subsets retain prognostic significance in uni- and multivariate analyses. Thus, if a SOCS1 mutation is present, the mutation type is an important single gene prognostic biomarker in DLBCL. Disclosures: No relevant conflicts of interest to declare.