title: SOCS1 mutation subtypes predict divergent outcomes in diffuse large B-Cell lymphoma (DLBCL) patients.
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.
authors.affiliation: Institute of Pathology, University of Ulm, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schif
authors.forename: Jochen K
authors.initials: JK
authors.lastname: Lennerz
authors.forename: Christian W
authors.initials: CW
authors.lastname: Kohler
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.forename: Ingo
authors.initials: I
authors.lastname: Melzner
authors.forename: Olga
authors.initials: O
authors.lastname: Ritz
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins