Kagan J, Finger L R, Letofsky J, Finan J, Nowell P C, Croce C M
Fels Institute for Cancer Research and Molecular Biology, Philadelphia, PA 19140.
Proc Natl Acad Sci U S A. 1989 Jun;86(11):4161-5. doi: 10.1073/pnas.86.11.4161.
The T-cell receptor (TCR) alpha/delta chain locus on chromosome 14q11 is nonrandomly involved in translocations and inversions in human T-cell neoplasms. We have analyzed three acute T-lymphoblastic leukemia samples carrying a t(10;14)(q24;q11) chromosome translocation by means of somatic cell hybrids and molecular cloning. In all cases studied the translocation splits the TCR delta chain locus. Somatic cell hybrids containing the human 10q+ chromosome resulting from the translocation retain the human terminal deoxynucleotidyltransferase gene mapped at 10q23-q24 and the diversity and joining, D delta 2-J delta 1, regions of the TCR delta chain, but not the V alpha region (variable region of the TCR alpha chain), demonstrating that the split occurred within the V alpha-D delta 2 region. Molecular cloning of the breakpoint junctions revealed that the TCR delta chain sequences involved are made from the D delta 2 segment. The chromosome breakpoints are clustered within a region of approximately 263 base pairs of chromosome 10. The results suggest that the translocation of the TCR delta chain locus to a locus on 10q, which we have designated TCL3, results in deregulation of this putative oncogene, leading to acute T-cell leukemia.
位于14q11染色体上的T细胞受体（TCR）α/δ链基因座在人类T细胞肿瘤的易位和倒位中被非随机涉及。我们通过体细胞杂交和分子克隆分析了三个携带t(10;14)(q24;q11)染色体易位的急性T淋巴细胞白血病样本。在所有研究的病例中，易位均使TCRδ链基因座发生断裂。由易位产生的含有人类10q+染色体的体细胞杂交体保留了定位于10q23 - q24的人类末端脱氧核苷酸转移酶基因以及TCRδ链的多样性和连接区Dδ2 - Jδ1，但不保留Vα区（TCRα链的可变区），这表明断裂发生在Vα - Dδ2区域内。对断点连接的分子克隆显示，所涉及的TCRδ链序列由Dδ2区段组成。染色体断点聚集在10号染色体约263个碱基对的区域内。结果表明，TCRδ链基因座易位至我们命名为TCL3的10q上的一个基因座，导致该假定癌基因的失调，进而引发急性T细胞白血病。
