Tosi Sabrina, Hughes Jim, Scherer Stephen W, Nakabayashi Kazuhiko, Harbott Jochen, Haas Oskar A, Cazzaniga Giovanni, Biondi Andrea, Kempski Helena, Kearney Lyndal
MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Genes Chromosomes Cancer. 2003 Oct;38(2):191-200. doi: 10.1002/gcc.10258.
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.
t(7;12)(q36;p13)是婴儿白血病中一种常见的染色体异常。在这些病例中，几个研究小组报告了ETV6基因的参与，该基因在其5'端始终发生破坏。在一些（但不是全部）报告的t(7;12)病例中检测到了ETV6与HLXB9之间的融合转录本。我们在此报告一项基于荧光原位杂交（FISH）对7例患者易位断点进行定位的研究，以及对其中2例患者使用Southern印迹法进行的详细分子研究。FISH研究显示，在HLXB9基因近端的一个黏粒重叠群内存在断点簇。Southern印迹分析使我们能够在两名患者中黏粒重叠群覆盖的区域内确定两个不同的断点。对一例不寻常的t(7;12)(q22;p13)病例[完整核型：46,XX,der(7)t(7;12)(q22;p13)del(7)(q22q36)]的分析也显示7q36处有一个断点，尽管位于与重叠黏粒相邻的区域。一名患者的5' RACE PCR显示涉及未参与t(7;12)的ETV6等位基因发生了重排，提示该病例可能不存在功能性ETV6等位基因。这些数据表明7q36处断点的分布存在一定异质性，这表明融合基因的产生可能不是t(7;12)白血病发生的机制，至少在某些情况下如此。
