The impact of SOCS1 mutations in diffuse large B‐cell lymphoma

Autor: 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, Peter Møller
Rok vydání: 2019
Předmět:
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
Zdroj: British Journal of Haematology
ISSN: 1365-2141
0007-1048
Popis: 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
Databáze: OpenAIRE
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