基因组检测综合分析在骨髓增生异常综合征诊治中的应用

本研究通过1例骨髓增生异常综合征（MDS）患者综合的分析，探讨基因组检测综合信息在MDS诊断、治疗方案选择以及预后评估的意义；采用核型分析、荧光原位杂交（FISH）及基于单核苷酸多态性的高分辨基因芯片分析（SNP—Array）检测患者染色体变化，采用新一代测序技术（NGS）检测患者的50肿瘤相关基因热点突变，对MDS的患者基因组信息进行综合分析。结果表明，G-带骨髓染色体核型分析检测到5号染色体长臂部分缺失和11号染色体长臂部分缺失，并得到FISH检测结果确认。SNP基因组芯片分析检测到两处获得性基因组大片段缺失，81Mb的5号染色体长臂中间缺失以及24Mb的11号染色体长臂中间缺失及2处获得性杂合缺失，分别是58Mb的1号染色体的短臂末端和39Mb14号染色体长臂末端。此外，孙驴基因组芯片分析检测到多条染色体的多个区域存在胚系发生的连续的大片段杂合性缺失，约占常染色体￡．因组的5．86％，提示患者父母具有3级亲属的血缘关系。50肿瘤基因热点突变检测未检出明显临床意义的基因突变信息，但在其中的6个基因中发现了6个基因位点的多态性，包括APC，FGFR3，KDR，KIT，PDGFRA和RET。结论：多种基因组学检测技术并用为患者提供了基因组学异常的全貌，其中一些发现对于患者的诊断、治疗方案的选择和预后很有意义，同时胚系基因组中存在的大片段杂合性缺失为遗传咨询提供有用的信息，也为MDS发病机制的研究提供线索。

Comprehensive Analysis of Genomic Detection for a Patient with Myelodysplastic Syndrome

This study was purposed to investigate the significance of genomic comprehensine analysis information in diagnosis, therapy and prognosis of MDS through comprehensive analysis of a patient with MDS. The bone marrow specimen from a patient with MDS was comprehensively analyzed by a combination of genomic approaches, including chromosomal karyotyping, fluorescence in situ hybridization （FISH）, genome scanning using Affymetrix high density SNP microarray platform, and next-generation sequencing （NGS） analysis using IonTorrent Cancer Gene Panel. The results showed that an abnormal clone was identified by standard G-banding karyotyping and confirmed by FISH, which contains interstitial deletions on the long arms of chromosome 5 and 11 respectively. SNP-array analysis defined the two genomic deletions to be an 81 Mb interstitial deletion on the long are of chromosome 5 and a 24 Mb interstitial deletion on the long are of chromosome 11. Meanwhile, SNP-array detected two genomic regions with acquired loss of heterozygosity （LOH）, a 58 Mb region on the short arm of chromosome 1 and a 39 Mb region on the distal end of the long arm of chromosome 14. In addition, SNP-array identified multiple genomic regions with long stretch of absence of heterozygosity, representing about 5.3 % of autosomal genome, indication a certain level of consanguinity between the parents. No clinically significant gene mutation was identified using IonTorrent 50 Cancer Gene Panel while 6 polymorphisms within 6 genes were observed including APC, FGFR3, KDR, KIT, PDGFRA, and RET. It is concluded that the combined genomic techniques are necessary to provide a full picture of the patient＇s genomic alterations. Some of the acquired genomic findings are important for the diagnosis and therapy selection. Germline genomic alterations warrant genetic counseling and are useful for further studies to explore the mechanisms leading to tumorigenesis of MDS patient.