title: MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma.
abstract: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is characterized by frequent central nervous system recurrence and a predominant activated B-cell-like nature. Primary DLBCL in sanctuary sites (DLBCL-SS) also demonstrates these features, and >70% of patients harbor myeloid differentiation primary response 88 (MYD88) (L265P) and CD79B mutations. The objective of the current study was to elucidate a possible relationship between CD5+DLBCL and DLBCL-SS.
  
  
  
  MYD88, CD79B, CD79A, and caspase recruitment domain family member 11 (CARD11) mutations were examined in samples from 40 patients with CD5+DLBCL. Mutation analysis was performed by direct sequencing.
  
  
  
  MYD88 and CD79B mutations were detected in 33% (13 patients) and 38% (15 patients), respectively, of the 40 patients with CD5+DLBCL. Ten patients had these 2 gene mutations, and 1 had a CD79A mutation. One of 2 patients with testicular involvement had both MYD88 and CD79B mutations. The other patient had a MYD88 mutation alone. None of the 31 patients examined was found to have a CARD11 mutation. MYD88 and CD79B mutations were found to be associated with localized disease (P = .038 and P = .003, respectively). Primary extranodal lymphoma was associated with higher frequencies of mutations in MYD88 or both MYD88 and CD79B (P = .008 and P = .014, respectively). There was no significant difference in overall survival based on MYD88 and CD79B mutation status.
  
  
  
  The incidence of MYD88 and CD79B mutations in patients with CD5+DLBCL is lower than that in patients with DLBCL-SS, suggesting that CD5+DLBCL is not the same disease as DLBCL-SS in terms of gene mutation status. CARD11 mutations are rare in patients with CD5+DLBCL. Cancer 2017;123:1166-1173. © 2016 American Cancer Society.
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Tawara
authors.affiliation: Pathology Division, Mie University Hospital, Tsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imai
authors.affiliation: Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ono
authors.affiliation: Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
authors.affiliation: Department of Endoscopy, Mie University Hospital, Tsu, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D018956:CD5 Antigens / Q000378:metabolism*; D051925:CD79 Antigens / Q000235:genetics*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004317:Doxorubicin / Q000627:therapeutic use; D056726:Genetic Association Studies; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010641:Phenotype; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D053468:CARD Signaling Adaptor Proteins; D018956:CD5 Antigens; D051925:CD79 Antigens; D053594:Myeloid Differentiation Factor 88; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; C426242:CARD11 protein, human; D006162:Guanylate Cyclase; D011241:Prednisone
keywords: CARD11 (caspase recruitment domain family member 11); CD5; CD79B; MYD88 (myeloid differentiation primary response 88); diffuse large B-cell lymphoma