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涉及T细胞受体α链基因与MYC 3'端序列的人染色体8;14易位断点连接的分子克隆。

Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor alpha-chain gene and sequences on the 3' side of MYC.

作者信息

McKeithan T W, Shima E A, Le Beau M M, Minowada J, Rowley J D, Diaz M O

出版信息

Proc Natl Acad Sci U S A. 1986 Sep;83(17):6636-40. doi: 10.1073/pnas.83.17.6636.

Abstract

The MOLT-16 cell line, which was established from the malignant cells of a patient with T-cell acute lymphoblastic leukemia, is characterized by a translocation involving chromosome 8 (band q24) and chromosome 14 (band q11) [t(8;14)(q24;q11)]. To determine the position of the gene encoding the alpha chain of the T-cell receptor and of the protooncogene MYC (formerly c-myc) in relation to the breakpoint junction and to evaluate their possible role in the pathogenesis of T-cell neoplasia, we applied the techniques of in situ chromosomal hybridization, Southern blot analysis, and molecular cloning to MOLT-16 cells. Our results indicate that the breakpoint on chromosome 14 at band q11 occurs close to a joining sequence of the gene encoding the alpha chain of the T-cell receptor. The constant region and part of the joining region of this gene are translocated to the 3' side of the MYC exons. The breakpoints on chromosomes 8 and 14 are close to, but distinct from, those found in SKW-3, another T-cell leukemia cell line, which has a t(8;14). The identification of a breakpoint to the 3' side of MYC suggests that this recurring translocation is analogous to the variant t(2;8) and t(8;22) translocations observed in the B-cell malignancies.

摘要

MOLT-16细胞系源自一名T细胞急性淋巴细胞白血病患者的恶性细胞,其特征是涉及8号染色体(q24带)和14号染色体(q11带)的易位[t(8;14)(q24;q11)]。为了确定编码T细胞受体α链的基因和原癌基因MYC(以前称为c-myc)相对于断点连接的位置,并评估它们在T细胞肿瘤发生机制中的可能作用,我们对MOLT-16细胞应用了原位染色体杂交、Southern印迹分析和分子克隆技术。我们的结果表明,14号染色体q11带的断点发生在靠近编码T细胞受体α链的基因的连接序列处。该基因的恒定区和部分连接区易位到MYC外显子的3'端。8号和14号染色体上的断点与另一个具有t(8;14)的T细胞白血病细胞系SKW-3中的断点接近但不同。在MYC的3'端鉴定出一个断点表明,这种反复出现的易位类似于在B细胞恶性肿瘤中观察到的变异t(2;8)和t(8;22)易位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c942/386559/b451b8ff90e9/pnas00321-0413-a.jpg

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