Heterogeneity of the 7q36 breakpoints in the t(7;12) involving ETV6 in infant leukemia
Heterogeneity of the 7q36 breakpoints in the t(7;12) involving ETV6 in infant leukemia
复制标题
DOI：
10.1002/gcc.10258
复制
发表时间：
2003-10-01
影响因子：
3.7
通讯作者：
Kearney, L
中科院分区：
文献类型：
--
作者：
Tosi, S;Hughes, J;Kearney, L
t(7;12)（q36;p13）是婴儿白血病中一种复发性染色体异常。在这些病例中，几个研究小组已经报道了ETV6的参与，并在其5'端持续破坏基因。在一些报道的t病例中发现了ETV6和HLXB9的融合转录物（7;12）。我们在此报告了一项基于荧光原位杂交（FISH）定位7例患者易位断点的研究，并对其中2例患者使用Southern印迹进行了详细的分子研究。FISH研究显示，在靠近HLXB9基因的cosmid中存在一组断点。南方印迹分析使我们能够在两个患者的cosmid覆盖的区域内定义两个不同的断点。对一个不寻常的病例t(7;12)(q22;p13)[全核型：46，XX,der(7)t(7; 12)(q22;p13)del(7)(q22q36)]的分析也显示了7q36的断裂，尽管在重叠的子体附近的区域。1例患者的5′RACE PCR显示，与t无关的ETV6等位基因出现重排（7;12），这表明该病例中可能不存在功能性ETV6等位基因。这些数据显示7q36中断点分布存在一定的异质性，表明融合基因的产生可能不是t细胞白血病发生的机制（7;12），至少在某些情况下是这样。(C) 2003 Wiley-Liss, Inc。
The t(7;12)(q36;p13) is a recurrent chromosome abnormality in infant leukemia. In these cases, the involvement of ETV6, with disruption of the gene consistently at its 5' end, has been reported by several groups. A fusion transcript between ETV6 and HLXB9 has been detected in some, but not all, reported cases of t(7;12). We report here a study based on fluorescence in situ hybridization (FISH) mapping of the translocation breakpoints in seven patients and detailed molecular studies using Southern blotting on two of these patients. The FISH studies have shown a cluster of breakpoints within a cosmid contig proximal to the HLXB9 gene. Southern blotting analysis enabled us to define two distinct breakpoints within the area covered by the cosmid contig in two patients. The analysis of an unusual case of t(7;12)(q22;p13) [full karyotype: 46,XX,der(7)t(7; 12)(q22;p13)del(7)(q22q36)] also revealed a break in 7q36, although in a region proximal to the overlapping cosmids. 5' RACE PCR in one patient has shown a rearrangement involving the ETV6 allele not involved in the t(7;12), suggesting that no functional ETV6 allele might be present in this case. These data show some heterogeneity in the distribution of breakpoints in 7q36, indicating that the generation of a fusion gene might not be the mechanism responsible for leukemogenesis in the t(7;12), at least in some cases. (C) 2003 Wiley-Liss, Inc.