NUCLEOTIDE-SEQUENCE OF A T(14,18) CHROMOSOMAL BREAKPOINT IN FOLLICULAR LYMPHOMA AND DEMONSTRATION OF A BREAKPOINT-CLUSTER REGION NEAR A TRANSCRIPTIONALLY ACTIVE LOCUS ON CHROMOSOME-18
NUCLEOTIDE-SEQUENCE OF A T(14,18) CHROMOSOMAL BREAKPOINT IN FOLLICULAR LYMPHOMA AND DEMONSTRATION OF A BREAKPOINT-CLUSTER REGION NEAR A TRANSCRIPTIONALLY ACTIVE LOCUS ON CHROMOSOME-18
复制标题
DOI：
10.1073/pnas.82.21.7439
复制
发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
SKLAR, J
中科院分区：
文献类型：
--
作者：
CLEARY, ML;SKLAR, J
滤泡性淋巴瘤的t(14;18)（q32;21）染色体易位特征是已知与任何特定类型的淋巴细胞恶性肿瘤相关的最常见的细胞遗传学异常。从携带这种易位的滤泡性淋巴瘤患者的肿瘤细胞中克隆出含有14号和18号染色体交叉点的DNA片段。断裂点DNA的核苷酸序列分析表明，14号染色体的断裂发生在无功能免疫球蛋白重链等位基因的连接区4 （J4）。这一发现以及该淋巴瘤中断点与功能多样性区-连接区（D-J）关节的其他结构相似性表明，D-J重组酶在t（14;18）易位机制中发挥了作用。对40例滤泡性淋巴瘤的DNA进行杂交分析，发现大多数t（14;18）易位发生在克隆断点4.2千碱基以内的18号染色体DNA上。从这个断点簇区提取的DNA探针可以在其克隆的肿瘤细胞和含有t（14;18）易位的b淋巴瘤细胞系中检测转录产物。
The t(14;18)(q32;21) chromosomal translocation characteristic of follicular lymphomas is the most common cytogenetic abnormality known to be associated with any specific type of hematolymphoid malignancy. A fragment of DNA containing the crossover point between chromosomes 14 and 18 was cloned from the tumor cells of a patient with a follicular lymphoma carrying this translocation. Nucleotide sequence analysis of the breakpoint DNA revealed that the break in chromosome 14 occurred in joining region 4 (J4) of the nonfunctional immunoglobulin heavy chain allele. This finding and other structural similarities of the breakpoint with the functional diversity region-joining region (D-J) joint in this lymphoma suggest that D-J recombination enzymes played a role in the mechanism of the t(14;18) translocation. Hybridization analysis of DNA from 40 follicular lymphomas showed that the majority of t(14;18) translocations occur on chromosome 18 DNA within 4.2 kilobases of the cloned breakpoint. A DNA probe from this breakpoint-cluster region detects transcription products in the tumor cells from which it was cloned and in a B-lymphoma cell line containing a t(14;18) translocation.