伴ins（13；8）（q12；p11p23）8p11骨髓增殖综合征一例报告及其受累基因的研究

Clinical and gene involved of one case of 8p11 myeloproliferative syndrome with ins （13;8） （q12;pllp23）

目的提高对伴有染色体插入易位ins（13；8）（q12；p11p23）形成ZNF198．FGFR1融合基因的罕见疾病8p11骨髓增殖综合征（EMS）的认识，并对该融合基因进行全长克隆及结构分析。方法报道1例伴ins（13；8）（q12；p11p23）形成ZNF198．FGFR1融合基因的EMS患者的临床表现、实验室特征及诊治经过，并通过重叠PCR及TA克隆对该融合基因进行全长扩增及克隆测序。结果常规染色体核型分析发现1例ins（13；8）（q12；p11p23）患者，其临床特征主要为外周血白细胞计数明显升高、髓系高度增生、淋巴结肿大、快速向白血病转化趋势等；荧光原位杂交显示FGFR1基因重排，RT-PCR及直接测序证实ZNF198-FGFR1融合基因阳性，对该融合基因全长克隆及克隆测序证实其保留了各自的主要功能结构域。结论染色体插入易位ins（13；8）（q12；p11p23）形成ZNF198-FGFR1融合基因，该融合基因保留了主要功能结构域，伴有该基因阳性患者具有独特的实验室及临床特征。

Objective To improve the understanding of patients with 8pll myeloproliferative syndrome （EMS） harboring ins （13;8） （q12;pllp23）/ZNF198-FGFR1. Methods We reported here a 8p 11 EMS case and provided more details on the clinical and molecular features of ins （ 13 ;8） （q 12;p 11 p23 ）/ ZNF198-FGFR1, full length ZNF198-FGFR1 was cloned by overlap extension PCR method, and the literatures on this topic were reviewed. Results Clinically, the case with ins（13;8） （q12;p11p23）/ZNF198- FGFR1 had distinct hematological and clinical characteristics： hyperleukocytosis, myeloid hyperplasia, widespread adenopathy and lymphoma; Fluorescence in situ hybridization （FISH） disclosed the positive FGFR1 gene rearrangement; Further molecular studies confirmed a mRNA in-frame fusion between exon 17 of the ZNFI98 gene and exon 9 of FGFR1 gene , the full length ZNF198-FGFR1 was composed of a NH2 terminus of ZNF198 including the ZNF and proline-rich domains, whereas the COOH terminus of FGFR1 included 2 tyrosine kinase domains. Conclusion EMS with ins（13;8） （q12;pllp23）/ZNF198- FGFR1 was a very rare, distinct myeloproliferative neoplasm, the fusion gene and chimeric protein with constitutive activation of the FGFR1 tyrosine kinase.