TRANSLOCATION OF C-MYC INTO THE IMMUNOGLOBULIN HEAVY-CHAIN LOCUS IN HUMAN ACUTE B-CELL LEUKEMIA - A MOLECULAR ANALYSIS
TRANSLOCATION OF C-MYC INTO THE IMMUNOGLOBULIN HEAVY-CHAIN LOCUS IN HUMAN ACUTE B-CELL LEUKEMIA - A MOLECULAR ANALYSIS
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DOI：
10.1002/j.1460-2075.1986.tb04302.x
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发表时间：
1986-05-01
期刊：
影响因子：
11.4
通讯作者：
PESCHLE, C
中科院分区：
文献类型：
--
作者：
CARE, A;CIANETTI, L;PESCHLE, C
我们报告了四例人类B细胞恶性肿瘤的原代细胞的分子分析，每一例都有8；14染色体易位，涉及c-myc原癌基因和免疫球蛋白(Ig)基因簇。在两例B细胞急性淋巴细胞白血病(B-ALL)中，c-myc基因被截短，重排到Ig Cα1基因，并在apprx的两个异常mRNAs中过度表达。2.0和2.8 kb。相反，在2例进展为白血病的B细胞淋巴瘤中，c-myc基因座在其编码和5‘-’侧翼区被完整地移位到不同于Cα1的Ig区，并在两种正常的mRNA物种中过度表达。对其中一例B-ALL的14Q+染色体断裂区的克隆和测序表明，myc基因在翻译起始点上游被截短1077个核苷酸，并以相反的转录方向重排为Ig类开关片段.apprx。位于C.alpha.1基因上游4.8kb。C-myc反义链在8号染色体断裂点的直接边界上含有两个类开关重组共识序列：这使得我们可以假设Ig和myc序列之间错误的类开关样重组导致了染色体易位。此外，我们报告了从易位的c-myc基因的第一内含子到第二外显子的区域内聚集的13个点突变，其中5个点突变导致氨基酸变化导致异常的myc蛋白。这是原发肿瘤细胞中c-myc易位突变的第一个证据。
We report the molecular analysis of primary cells from four cases of human B-cell malignancies each with an 8;14 chromosomal translocation involving the c-myc proto-oncogene and the immunoglobulin (Ig) gene cluster. In two cases of B-cell acute lymphocytic leukemia (B-ALL) the c-myc is truncated, rearranged into the Ig C.alpha.1 locus and over-expressed in two abnormal mRNAs of .apprx. 2.0 and 2.8 kb. Conversely, in two cases of B-cell lymphoma progressed into leukemia the c-myc locus was translocated intact in its coding and 5''-flanking region into an Ig region different from C.alpha.1, and over-expressed in two normal mRNA species. Cloning and sequencing of the breakpoint region on chromosome 14q+ from one of the two B-ALL cases showed that the myc gene is truncated 1077 nucleotides upstream from the translation start site, and rearranged in the opposite transcriptional orientation into an Ig class-switch segment .apprx. 4.8 kb upstream from the C.alpha.1 gene. The c-myc anti-sense strand contains two class-switch recombination consensus sequences in the immediate boundaries of the breakpoint on chromosome 8: this allows us to postulate that an erroneous, class-switch-like recombination between Ig and myc sequences gave rise to the chromosomal translocation. Furthermore, we report 13 point mutations clustered in a region spanning from the first intron to the second exon of the translocated c-myc gene, five of which cause amino acid changes leading to an abnormal myc protein. This is the first evidence of mutations in a translocated c-myc in primary tumor cells.