Shiramizu B, Barriga F, Neequaye J, Jafri A, Dalla-Favera R, Neri A, Guttierez M, Levine P, Magrath I
Pediatric Branch, National Cancer Institute, Bethesda, MD 20892.
Blood. 1991 Apr 1;77(7):1516-26.
We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5' region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations.
我们通过Southern印迹法研究了55例伯基特淋巴瘤（BL）的染色体断点位置模式，涉及地理分布和爱泼斯坦-巴尔病毒（EBV）关联情况。我们证实了8号染色体断点与地理分布之间的关联：74%的地方性伯基特淋巴瘤（eBL），但只有9%的散发性伯基特淋巴瘤（sBL）在包含c-myc基因的HindIII片段之外有断点（P2小于0.00001）。相反，91%的sBL显示出HindIII片段重排，而且与17%的eBL病例相比，这些病例中至少56%在c-myc的第一个外显子或内含子内有断点（P2小于0.004）。14号染色体上开关μ（Sμ）区域（即包含Sμ的HindIII片段）之外的断点总体上是Sμ区域内断点（27%）的两倍（73%），但在15个有Sμ断点的肿瘤中，13个（87%）有c-myc基因重排。8号染色体上包含c-myc的HindIII片段之外的断点主要与14号染色体上非Sμ断点相关（85%），这是与eBL最常相关的组合（65%；sBL为6%，P2小于0.00001）。在sBL中，最常见的断点组合是c-myc基因重排与非Sμ断点（63%；eBL为13%）。28%的sBL和13%的eBL在c-myc和Sμ内都有断点。EBV DNA在20个c-myc之外有断点的肿瘤中的19个中存在，在7个c-myc紧邻5'区域有断点的肿瘤中均不存在，在5个第一个外显子有断点的肿瘤中的4个中存在，在12个第一个内含子有断点的肿瘤中的7个中存在。这些数据表明，eBL和sBL的发病机制在c-myc失调机制方面存在差异，可能在恶性转化靶细胞的分化状态方面也存在差异。我们针对EBV在发病机制中的潜在作用提出了一个可检验的假设：即在存在某些（但不是所有）由染色体易位引起的c-myc损伤类型时，它需要促成c-myc的失调。
