1. The impact of SOCS1 mutations in diffuse large B‐cell lymphoma
- Author
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Wolfram Klapper, Lorenz Trümper, Martin-Leo Hansmann, Norbert Schmitz, Jochen K. Lennerz, Markus Löffler, Marita Ziepert, Melanie Martin, Annette M. Staiger, Harald Stein, Manuel Lüdeke, Alfred C. Feller, Andreas Rosenwald, Markus Kreuz, Kevin Mellert, Sylvia Hartmann, German Ott, and Peter Møller
- Subjects
Male ,Oncology ,DNA Mutational Analysis ,Kaplan-Meier Estimate ,CHOP ,Cohort Studies ,0302 clinical medicine ,Mutation Rate ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,SOCS1 ,Mutation frequency ,Exome ,Aged, 80 and over ,Haematological Malignancy ,Age Factors ,R-CHOP ,diffuse large B-cell lymphoma ,DNA, Neoplasm ,Hematology ,Middle Aged ,Prognosis ,Neoplasm Proteins ,3. Good health ,Treatment Outcome ,Vincristine ,030220 oncology & carcinogenesis ,Cohort ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,Research Paper ,medicine.drug ,medicine.medical_specialty ,Genotype ,Prednisolone ,03 medical and health sciences ,Suppressor of Cytokine Signaling 1 Protein ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Cyclophosphamide ,Aged ,business.industry ,diffuse large B‐cell lymphoma ,medicine.disease ,Lymphoma ,Doxorubicin ,Mutation ,R‐CHOP ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
Mutations in SOCS1 are frequent in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma. In the latter, SOCS1 mutations affect the length of the encoded protein (major mutations) and are associated with shorter patient survival. Two independent studies examined the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and showed differing results. This may be due to the small number of included patients, the heterogeneity of patients' demographics and the distinct treatment schemes in these studies. To overcome the size limitations of these previous studies, we assessed SOCS1 mutations in the RICOVER-60 cohort. The cohort uniformly consists of elderly patients (aged 61-80 years) treated with the CHOP-14 scheme (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone at 14-day intervals) with or without an additional rituximab treatment. Patient outcomes were analysed with regard to overall SOCS1 mutation frequency, major and minor mutations and a novel impact-based classifier - against the treatment modalities. Patients harbouring putative pathogenic SOCS1 mutations showed significant reduced overall survival within the CHOP plus rituximab group. Hence, putative pathogenic SOCS1 mutations seem to efface the beneficial effect of the therapeutic CD20 antibody. Comparing published data of whole exome and transcriptome sequencing of a large DLBCL cohort confirmed that predicted deleterious SOCS1 mutations forecast pre-eminent survival in early onset DLBCL. peerReviewed
- Published
- 2019