Takeuchi Toshifumi, Yamaguchi Motoko, Kobayashi Kyoko, Miyazaki Kana, Tawara Isao, Imai Hiroshi, Ono Ryoichi, Nosaka Tetsuya, Tanaka Kyosuke, Katayama Naoyuki
Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.
Pathology Division, Mie University Hospital, Tsu, Japan.
Cancer. 2017 Apr 1;123(7):1166-1173. doi: 10.1002/cncr.30404. Epub 2016 Dec 4.
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.
CD5阳性（CD5+）弥漫性大B细胞淋巴瘤（DLBCL）的特征是中枢神经系统复发频繁且主要为活化B细胞样性质。原发于免疫豁免部位的DLBCL（DLBCL-SS）也具有这些特征，超过70%的患者存在髓样分化主要反应88（MYD88）（L265P）和CD79B突变。本研究的目的是阐明CD5+ DLBCL与DLBCL-SS之间可能存在的关系。
对40例CD5+ DLBCL患者的样本进行MYD88、CD79B、CD79A和半胱天冬酶募集结构域家族成员11（CARD11）突变检测。通过直接测序进行突变分析。
在40例CD5+ DLBCL患者中，分别有33%（13例）和38%（15例）检测到MYD88和CD79B突变。10例患者有这两种基因突变，1例有CD79A突变。2例睾丸受累患者中，1例同时有MYD88和CD79B突变，另1例仅有MYD88突变。在检测的31例患者中均未发现CARD11突变。发现MYD88和CD79B突变与局限性疾病相关（分别为P = 0.038和P = 0.003）。原发性结外淋巴瘤与MYD88或MYD88和CD79B两者的较高突变频率相关（分别为P = 0.008和P = 0.014）。基于MYD88和CD79B突变状态的总生存期无显著差异。
CD5+ DLBCL患者中MYD88和CD79B突变的发生率低于DLBCL-SS患者，这表明就基因突变状态而言，CD5+ DLBCL与DLBCL-SS并非同一种疾病。CARD11突变在CD5+ DLBCL患者中罕见。《癌症》2017年；123：1166 - 1173。© 2016美国癌症协会
