Intraclonal molecular heterogeneity suggests a hierarchy of pathogenetic events in Burkitt's lymphoma
Intraclonal molecular heterogeneity suggests a hierarchy of pathogenetic events in Burkitt's lymphoma
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DOI：
10.1023/a:1008265304712
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发表时间：
1997-10-01
影响因子：
50.5
通讯作者：
Magrath, I
中科院分区：
文献类型：
--
作者：
Gutierrez, MI;Bhatia, K;Magrath, I
背景资料。伯基特淋巴瘤是一种B细胞肿瘤，其特征是染色体易位，涉及c-myc基因。除c-myc易位外，bl还可携带其他几种病变，包括a)c-myc突变，b)bcl6突变，c)p53突变和d)EBV基因组突变。在这份报告中，我们描述了一项独特的研究，即在Burkitt淋巴瘤的演变和进展过程中，这些遗传损害的发生时间。材料和方法。从两名Burkitt淋巴瘤患者中的每一位，我们建立了三个不同的细胞系--来自疾病的不同部位或在疾病的临床过程(诊断和复发)的不同时间。染色体核型分析，Southern印迹、聚合酶链式反应、单链构象多态性分析和序列分析确定是否存在分子损伤。在每个患者中，所有克隆都携带相同的c-myc易位、相同的bcl6状态(野生型或突变型)和相同的VDJ重排。结论：c-myc易位和bcl6基因突变可能是早期事件，c-myc编码区突变发生较早，而p53基因突变可能发生较晚。在一例HIV相关性Burkitt淋巴瘤的细胞系中观察到反映独立EBV感染的离散克隆带，这表明EBV感染可能是一种晚期事件，至少在某些HIV相关性淋巴瘤中是如此。
Background. Burkitt's lymphoma is a B-cell neoplasm characterized by a chromosomal translocation involving the c-myc gene. BL may carry, besides the c-myc translocation, several other lesions including a) mutations in c-myc, b) mutations in bcl-6, c) mutations in p53 and d) EBV genomes. In this report we describe a unique study of the timing of these genetic lesions during the evolution and progression of Burkitt's lymphoma.Materials and methods. From each of two patients with Burkitt's lymphoma, we established three different cell lines - from different sites or at different times in the clinical course of the disease (diagnosis and relapse). Chromosomal aberrations were analyzed by karyotyping and the presence of molecular lesions determined by Southern blot, PCR, SSCP and sequence analyses.Results. In each patient all the clones carry identical c-myc translocations, identical bcl-6 status (wild type or mutant) and the same productive VDJ rearrangement. However, within each individual patient, we could demonstrate the presence of intraclonal variation with respect to EBV, p53 mutations and c-myc mutations.Conclusions: c-myc translocation and bcl-6 mutations appear to be early events, mutations in the coding region of c-myc occur early but are an ongoing event, while mutations in the p53 gene seem to occur later. Discrete clonal bands reflecting independent EBV infection were observed in the cell lines from one HIV-associated Burkitt's lymphoma, suggesting the possibility that EBV infection may occur as a late event, at least in some HIV associated lymphomas.