Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.

Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.
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与非霍奇金淋巴瘤临床转化相关的连续 bcl-2 和 c-myc 癌基因重排。

DOI:
10.1172/jci114320
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发表时间:
1989
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Williams,ME
Williams,ME
中科院分区:
--
文献类型:
--
作者:
Lee,JT;InnesJr,DJ;Williams,ME

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我们报告一个未经治疗的非何杰金氏淋巴瘤的病例,其组织学进展超过1年,从低级别、小裂滤泡中心细胞淋巴瘤发展为高级别、小无裂滤泡中心细胞淋巴瘤。这两个淋巴瘤有相同的免疫球蛋白(IG)重链连接基因(JH),κ轻链连接基因,和bcl-2基因重排,表明克隆的身份,这两个肿瘤。一条14号染色体上的IG重链基因座参与初始t(14; 18)易位,如通过共迁移JH和bcl-2重排所示。然而,癌基因c-myc在最初的淋巴瘤中处于种系构型,但在高级别肿瘤中,在外显子I的3'末端附近有一个等位基因重排; DNA序列分析与该位点的染色体断裂点一致。c-myc重排在高级别肿瘤中的存在表明c-myc在低级别肿瘤向更具侵袭性的淋巴瘤的克隆进化中起作用。bcl-2基因重排和c-myc癌基因重排在同一肿瘤中共存的情况并不多见,仅有少数病例报道。此外,该病例在直接证明与bcl-2基因和c-myc癌基因顺序重排相关的人类淋巴瘤的组织学和临床进展方面是独一无二的。图片
We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.Images
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