Ballerini P, Gaidano G, Gong J Z, Tassi V, Saglio G, Knowles D M, Dalla-Favera R
Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, NY 10032.
Blood. 1993 Jan 1;81(1):166-76.
Non-Hodgkin's lymphoma (NHL) develops in about 5% to 10% of acquired immunodeficiency syndrome (AIDS) patients. The vast majority of AIDS-NHL are clinically aggressive B-cell NHL that are histologically classified as small noncleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large noncleaved cell lymphoma (LNCCL). In an attempt to understand the molecular pathogenesis of these tumors, we have investigated the involvement of dominantly acting oncogenes (c-myc, N-, K-, H-Ras), tumor suppressor genes (p53, RB1), and Epstein-Barr virus (EBV) infection in 27 AIDS-NHL samples (16 SNCCL, 5 LC-IBP, and 6 LNCCL). The following lesions were detected in AIDS-NHL: EBV infection (10/24; 41.6%), c-myc rearrangement (19/24; 79.1%), Ras mutation (4/27; 14.8%), and p53 loss/mutation (10/27; 37.0%). These lesions are not uniformly distributed, but, rather, cluster with specific types of AIDS-NHL: EBV infection is preferentially associated with LC-IBPL (4/4; 100%), while it is present in only a fraction of SNCCL (5/16; 31.2%) and LNCCL (1/4; 25%); c-myc oncogene activation clusters with SNCCL (16/16; 100%), whereas it is less frequent in LC-IBPL (1/4; 25%) and LNCCL (2/4; 50%); p53 inactivation is restricted to SNCCL (10/16; 62.5%) and consistently associated with c-myc activation. These data show that AIDS-NHL are associated with multiple genetic lesions that involve both proto-oncogenes and tumor suppressor genes and may accumulate in the relatively short period of time (4 to 6 years) between human immunodeficiency virus infection and AIDS-NHL development. These genetic lesions differ in the various AIDS-NHL subtypes, suggesting the involvement of distinct molecular pathway.
非霍奇金淋巴瘤（NHL）在约5%至10%的获得性免疫缺陷综合征（AIDS）患者中发生。绝大多数AIDS相关NHL在临床上是侵袭性B细胞NHL，组织学上分类为小无裂细胞淋巴瘤（SNCCL）、大细胞免疫母细胞浆细胞样淋巴瘤（LC - IBPL）和大无裂细胞淋巴瘤（LNCCL）。为了试图理解这些肿瘤的分子发病机制，我们研究了显性作用癌基因（c - myc、N -、K -、H - Ras）、肿瘤抑制基因（p53、RB1）以及爱泼斯坦 - 巴尔病毒（EBV）感染在27例AIDS相关NHL样本（16例SNCCL、5例LC - IBP和6例LNCCL）中的情况。在AIDS相关NHL中检测到以下病变：EBV感染（10/24；41.6%）、c - myc重排（19/24；79.1%）、Ras突变（4/27；14.8%）以及p53缺失/突变（10/27；37.0%）。这些病变并非均匀分布，而是与特定类型的AIDS相关NHL聚集：EBV感染优先与LC - IBPL相关（4/4；100%），而仅在一部分SNCCL（5/16；31.2%）和LNCCL（1/4；25%）中存在；c - myc癌基因激活与SNCCL聚集（16/16；100%），而在LC - IBPL（1/4；25%）和LNCCL（2/4；50%）中频率较低；p53失活仅限于SNCCL（10/16；62.5%）且始终与c - myc激活相关。这些数据表明，AIDS相关NHL与涉及原癌基因和肿瘤抑制基因的多种基因病变相关，并且可能在人类免疫缺陷病毒感染与AIDS相关NHL发生之间相对较短的时间（4至6年）内积累。这些基因病变在不同的AIDS相关NHL亚型中有所不同，提示涉及不同的分子途径。
