title: Frequent MYD88 L265P and CD79B Mutations in Primary Breast Diffuse Large B-Cell Lymphoma.
abstract: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising <3% of extranodal lymphomas. It frequently reveals an activated B-cell (ABC)-like phenotype. ABC-like DLBCL was reported to have gain-of-function mutations in MYD88, CD79B, CARD11, and TNFAIP3, resulting in constitutive activation of the NFκB pathway. Because of the rare occurrence of PB-DLBCL, the frequency of MYD88 and CD79B mutations is still unknown. We used Sanger sequencing to study these mutations from 46 breast DLBCL cases and also investigated the associated clinicopathologic factors. MYD88 L265P was confirmed by allele-specific polymerase chain reaction and compared with the Sanger sequencing results. MYD88 L265P and CD79B mutations were detected in 27/46 (58.7%) and 11/33 (33.3%) cases, respectively. Twenty-eight of 46 cases met the criteria for PB-DLBCL, and the latter 18 cases were further classified as clinical breast DLBCL (CLB-DLBCL). The frequency of MYD88 L265P and CD79B mutations was 16/28 (57.1%) and 9/23 (39.1%), respectively, in PB-DLBCL and 11/18 (61.1%) and 2/10 (20%), respectively, in CLB-DLBCL. When the cutoff value was set at ΔCt≤1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.
authors.affiliation: *Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ∥Department of Pathology, Japanese Red Cross Okayama Hospital #Department of Hematology and Oncology, Okayama University Hospital, Okayama ‡Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya §Department of Diagnostic Pathology, School of Medicine, Fukushima Medical University, Fukushima ¶Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan †Department of Pathology, Chi-Mei Medical Center, Tainan and Taipei Medical University, Taipei, Taiwan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.forename: Shih-Sung
authors.initials: SS
authors.lastname: Chuang
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyata-Takata
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Satou
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Maiko
authors.initials: M
authors.lastname: Tamura
authors.forename: Keina
authors.initials: K
authors.lastname: Nagakita
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ohnishi
authors.forename: Mai
authors.initials: M
authors.lastname: Noujima-Harada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tabata
authors.forename: Yara Yukie
authors.initials: YY
authors.lastname: Kikuti
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D051925:CD79 Antigens / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007564:Japan; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D013624:Taiwan
chemical_list: D014408:Biomarkers, Tumor; D051925:CD79 Antigens; C497883:CD79B protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88