title: Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities.
abstract: STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell-specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non-B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.
authors.affiliation: Senckenberg Institute for Pathology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Mottok
authors.forename: Christoph
authors.initials: C
authors.lastname: Renné
authors.forename: Marc
authors.initials: M
authors.lastname: Seifert
authors.forename: Elsie
authors.initials: E
authors.lastname: Oppermann
authors.forename: Wolf
authors.initials: W
authors.lastname: Bechstein
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Andreas
authors.initials: A
authors.lastname: Bräuninger
mesh_terms: D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins