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非霍奇金淋巴瘤中的染色体断裂模式:对肿瘤发生中基因改变的意义

Patterns of chromosome breakage in nonHodgkin lymphoma: significance to gene alteration in tumorigenesis.

作者信息

Chaganti R S, Koduru P R

出版信息

Cytogenet Cell Genet. 1987;45(2):93-8. doi: 10.1159/000132436.

DOI:10.1159/000132436
PMID:3476255
Abstract

In a comprehensive cytogenetic analysis of nonHodgkin lymphoma (NHL) that was based on a database derived from karyotypic descriptions of 264 tumors, we previously established correlations between specific chromosome changes and histologic subtypes of lymphoma. In the present paper we analyze the total chromosome breakage encountered in this group of tumors. This analysis permitted distinction between sites of nonrandom breakage that are specific for lymphoid tumors (and hence of probable primary or etiologic significance) and sites of nonrandom breakage that are common to lymphoid as well as nonlymphoid tumors (and hence of probable secondary or evolutionary significance). We also observed that breakage affected all of the immunoglobulin and T cell receptor gene sites and most of the known cellular oncogene and fragile sites; however, only a limited number of these sites exhibited statistically significant breakage. Of special interest was the fact that the fragile sites that exhibited significant breakage were mostly those that also were sites of cellular oncogenes. Our data suggest that breakage at sites of immunoglobulin genes and a limited number of cellular oncogenes alone is of importance in B-cell lymphomagenesis. While the timing or causes of genomic destabilization in tumorigenesis are unknown, recent molecular analysis of junction regions of chromosome rearrangements designated here as primary translocations has suggested that more than one mechanism may be involved in their generation. This study identifies chromosomal sites of nonrandom perturbation that may be targeted for detailed molecular analysis aimed at understanding the origin, evolution, and spread of B-cell NHL.

摘要

在一项基于264例肿瘤核型描述数据库的非霍奇金淋巴瘤(NHL)综合细胞遗传学分析中,我们先前已建立了特定染色体变化与淋巴瘤组织学亚型之间的相关性。在本文中,我们分析了这组肿瘤中出现的总染色体断裂情况。该分析有助于区分淋巴样肿瘤特有的非随机断裂位点(因此可能具有主要或病因学意义)和淋巴样及非淋巴样肿瘤共有的非随机断裂位点(因此可能具有次要或进化意义)。我们还观察到,断裂影响了所有免疫球蛋白和T细胞受体基因位点以及大多数已知的细胞癌基因和脆性位点;然而,这些位点中只有少数表现出具有统计学意义的断裂。特别令人感兴趣的是,表现出显著断裂的脆性位点大多也是细胞癌基因的位点。我们的数据表明,仅免疫球蛋白基因位点和少数细胞癌基因的断裂在B细胞淋巴瘤发生中具有重要意义。虽然肿瘤发生过程中基因组不稳定的时间或原因尚不清楚,但最近对这里指定为原发性易位的染色体重排连接区域的分子分析表明,其产生可能涉及多种机制。本研究确定了非随机扰动的染色体位点,这些位点可能是旨在了解B细胞NHL起源、演变和扩散的详细分子分析的目标。

相似文献

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Patterns of chromosome breakage in nonHodgkin lymphoma: significance to gene alteration in tumorigenesis.非霍奇金淋巴瘤中的染色体断裂模式:对肿瘤发生中基因改变的意义
Cytogenet Cell Genet. 1987;45(2):93-8. doi: 10.1159/000132436.
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引用本文的文献

1
Molecular pathology of low grade malignant lymphomas.低度恶性淋巴瘤的分子病理学
Med Oncol. 1995 Sep;12(3):167-76. doi: 10.1007/BF01571194.
2
Cytogenetics of malignant lymphomas.
Blut. 1988 Sep;57(3):101-9. doi: 10.1007/BF00320147.