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

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.

Keywords: SOCS1; CHOP; R-CHOP; diffuse large B-cell lymphoma.