SOCS1 Mutation Subtypes Predict Divergent Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) Patients
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Birgit Schif1,*, Jochen K. Lennerz1,*, Christian W. Kohler2, Stefan Bentink2, Markus Kreuz3, Ingo Melzner1, Olga Ritz1, Lorenz Trümper4, Markus Loeffler3, Rainer Spang2, and Peter Möller1
1 Institute of Pathology, University of Ulm, Germany
2 Institute of Functional Genomics, University Regensburg, Germany
3 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany
4 Department of Hematology and Oncology, Georg-August-University Göttingen, Germany
* denotes equal contribution
Peter Möller, email:
Keywords: Lymphoma, DLBCL, SOCS1 mutation
Received: December 07, 2012, Accepted: December 09, 2012, Published: December 09, 2012
Suppressor of cytokine signaling 1 (SOCS1) is frequently mutated in primary mediastinal and diffuse large B-cell lymphomas (DLBCL). Currently, the prognostic relevance of these mutations in DLBCL is unknown. To evaluate the value of the SOCS1 mutation status as a prognostic biomarker in DLBCL patients, we performed full-length SOCS1 sequencing in tumors of 154 comprehensively characterized DLBCL patients. We identified 90 SOCS1 mutations in 16% of lymphomas. With respect to molecular consequences of mutations, we defined two distinct subtypes: those with truncating (major) and those with non-truncating mutations (minor), respectively. The SOCS1 mutated subgroup or the minor/major subtypes cannot be predicted on clinical grounds; however, assignment of four established gene-expression profile-based classifiers revealed significant associations of SOCS1 major cases with germinal center and specific pathway activation pattern signatures. Above all, SOCS1 major cases have an excellent overall survival, even better than the GCB-like subgroup. SOCS1 minor cases had a dismal survival, even worse than the ABC gene signature group. The SOCS1 mutation subsets retained prognostic significance in uni- and multivariate analyses. Together our data indicate that assessment of the SOCS1 mutation status is a single gene prognostic biomarker in DLBCL.
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