Wu X, Ivanova G, Merup M, Jansson M, Stellan B, Grandér D, Zabarovsky E, Gahrton G, Einhorn S
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Genomics. 1999 Sep 1;60(2):161-71. doi: 10.1006/geno.1999.5911.
The pathogenesis of hairy cell leukemia (HCL) remains largely unknown since no specific genetic lesion has been identified in this disease. Previous cytogenetic analysis from our group has shown that chromosome abnormalities involving the 5q13 band are common in HCL, occurring in approximately 1/3 of patients. The data suggest that the 5q13.3 band is likely to harbor a gene involved in the transformational events of this disease. We have recently found two cosmids flanking the 5q13.3 breakpoint in patients with HCL, and the distance between them is approximately 35 kb, as analyzed by fiber-FISH. The two cosmids have been located between the markers SGC34998 and WI-15505/WI-6897 by radiation hybrid mapping. Five of 11 patients with HCL had a hemizygous deletion of the two cosmids, indicating that the function of a tumor suppressor gene may be lost. With the aim of delineating the critical region of 5q13.3 loss in patients with HCL, we have constructed an integrated contig of YAC, BAC, PAC, P1, and cosmid clones that covers the region. Within this area, three expressed sequences were identified as candidates for the putative 5q13.3 tumor suppressor gene involved in the pathogenesis of HCL.
毛细胞白血病（HCL）的发病机制在很大程度上仍然未知，因为在这种疾病中尚未发现特定的基因损伤。我们团队之前的细胞遗传学分析表明，涉及5q13带的染色体异常在HCL中很常见，约1/3的患者会出现。数据表明，5q13.3带可能含有一个与该疾病转化事件相关的基因。我们最近在HCL患者中发现了两个位于5q13.3断点两侧的黏粒，通过纤维荧光原位杂交分析，它们之间的距离约为35 kb。通过辐射杂种图谱分析，这两个黏粒已定位在标记SGC34998和WI-15505/WI-6897之间。11例HCL患者中有5例存在这两个黏粒的半合子缺失，表明肿瘤抑制基因的功能可能丧失。为了确定HCL患者中5q13.3缺失的关键区域，我们构建了一个覆盖该区域的YAC、BAC、PAC、P1和黏粒克隆的整合重叠群。在这个区域内，三个表达序列被确定为参与HCL发病机制的假定5q13.3肿瘤抑制基因的候选基因。
