Wu X, Merup M, Juliusson G, Jansson M, Stellan B, Grandér D, Zabarovsky E, Liu Y, Spasokoukotskaja T, Gahrton G, Einhorn S
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Genes Chromosomes Cancer. 1997 Dec;20(4):337-46. doi: 10.1002/(sici)1098-2264(199712)20:4<337::aid-gcc4>3.0.co;2-2.
Previous cytogenetic analysis has indicated that chromosome anomalies involving the 5q13 band are common in hairy cell leukemia (HCL), occurring in approximately 1/3 of the patients. The data suggest that 5q13.3 is likely to harbor a gene involved in the transformational event of this disease. We selected a constitutional inv(5)(p13.1q13.3) in a patient with HCL as the starting point in an attempt to identify the relevant gene in 5q13.3. By using double color interphase fluorescence in situ hybridization (FISH) techniques, we have identified two cosmid probes from a chromosome 5-specific library that flank the 5q13.3 inversion breakpoint proximally and distally. Pulsed field gel electrophoresis (PFGE) and interphase FISH experiments suggest that the two markers are at a distance of no more than 300 kb. YAC probes covering a 21 Mb region at 5q13 were used to map the 5q13.3 inversion breakpoint and the breakpoint is located within the D5S646-D5S620 region. Two non-chimeric YACs have been identified that span the breakpoint. FISH analysis revealed that four other patients with cytogenetic aberrations of 5q carried inversions/deletions that involved the same 5q13.3 breakpoint region. The identification of a gene involved in hairy cell leukemogenesis in this region will be of major importance in the elucidation of the transformational events of HCL.
先前的细胞遗传学分析表明，涉及5q13带的染色体异常在毛细胞白血病（HCL）中很常见，约1/3的患者会出现。数据表明，5q13.3可能含有一个与该疾病转化事件相关的基因。我们选择了一名HCL患者的一条结构上倒位的inv(5)(p13.1q13.3)作为起点，试图鉴定5q13.3中的相关基因。通过使用双色间期荧光原位杂交（FISH）技术，我们从一个5号染色体特异性文库中鉴定出两个黏粒探针，它们在5q13.3倒位断点的近端和远端侧翼。脉冲场凝胶电泳（PFGE）和间期FISH实验表明，这两个标记物之间的距离不超过300 kb。使用覆盖5q13区域21 Mb的酵母人工染色体（YAC）探针来定位5q13.3倒位断点，该断点位于D5S646 - D5S620区域内。已经鉴定出两个跨越该断点的非嵌合YAC。FISH分析显示，另外四名具有5q细胞遗传学异常的患者携带的倒位/缺失涉及相同的5q13.3断点区域。在该区域鉴定出一个与毛细胞白血病发生相关的基因对于阐明HCL的转化事件将具有重要意义。
