SOCS1 Mutation Subtypes Predict Divergent Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) Patients
| Autor: | Birgit Schif, Peter Möller, Ingo Melzner, Rainer Spang, Markus Kreuz, Lorenz Trümper, Olga Ritz, Markus Loeffler, Jochen K. Lennerz, Christian W. Kohler, Stefan Bentink |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Oncology
Male Pathology Lymphoma DNA Mutational Analysis 610 Medizin Suppressor of Cytokine Signaling Proteins Kaplan-Meier Estimate SOCS1 mutation 0302 clinical medicine hemic and lymphatic diseases Epidemiology Outcome Assessment Health Care DLBCL 570 Biowissenschaften Biologie Child Aged 80 and over 0303 health sciences ddc:610 Hematology Middle Aged Prognosis 3. Good health Tumor Markers Biological 030220 oncology & carcinogenesis Child Preschool Mutation (genetic algorithm) Female ddc:570 Lymphoma Large B-Cell Diffuse Research Paper Adult medicine.medical_specialty ddc:500 Adolescent Mutation Missense Biology Polymorphism Single Nucleotide Outcome Assessment (Health Care) 03 medical and health sciences Young Adult Suppressor of Cytokine Signaling 1 Protein Internal medicine medicine Biomarkers Tumor Humans 030304 developmental biology Aged Suppressor of cytokine signaling 1 Gene Expression Profiling Germinal center Gene signature medicine.disease Mutation 500 Naturwissenschaften Diffuse large B-cell lymphoma Gene Deletion |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Birgit Schif 1,* , Jochen K. Lennerz 1,* , Christian W. Kohler 2 , Stefan Bentink 2 , Markus Kreuz 3 , Ingo Melzner 1 , Olga Ritz 1 , Lorenz Trumper 4 , Markus Loeffler 3 , Rainer Spang 2 , and Peter Moller 1 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 Gottingen, Germany * denotes equal contribution Correspondence: Peter Moller, email: // Keywords : Lymphoma, DLBCL, SOCS1 mutation Received : December 07, 2012, Accepted : December 09, 2012, Published : December 09, 2012 Abstract 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. |
| Databáze: | OpenAIRE |
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