The impact of SOCS1 mutations in diffuse large B-cell lymphoma.
Age Factors
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ genetics
Cohort Studies
Cyclophosphamide
/ therapeutic use
DNA Mutational Analysis
/ methods
DNA, Neoplasm
/ genetics
Doxorubicin
/ therapeutic use
Female
Genotype
Humans
Kaplan-Meier Estimate
Lymphoma, Large B-Cell, Diffuse
/ drug therapy
Male
Middle Aged
Mutation
Mutation Rate
Neoplasm Proteins
/ genetics
Prednisolone
/ therapeutic use
Prognosis
Rituximab
/ administration & dosage
Suppressor of Cytokine Signaling 1 Protein
/ genetics
Treatment Outcome
Vincristine
/ therapeutic use
SOCS1
CHOP
R-CHOP
diffuse large B-cell lymphoma
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
15
03
2019
accepted:
11
06
2019
pubmed:
14
8
2019
medline:
23
6
2020
entrez:
14
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31407320
doi: 10.1111/bjh.16147
pmc: PMC6899586
doi:
Substances chimiques
Biomarkers, Tumor
0
DNA, Neoplasm
0
Neoplasm Proteins
0
SOCS1 protein, human
0
Suppressor of Cytokine Signaling 1 Protein
0
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
Prednisolone
9PHQ9Y1OLM
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
627-637Informations de copyright
© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
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