非特指型外周T细胞淋巴瘤FGR和TP73基因改变的研究

目的 研究非特指型外周T细胞淋巴瘤(PTCL-NOS)中FGR和TP73的基因改变,验证前期基于芯片的比较基因组杂交(a-CGH)研究结果,为PTCL-NOS的发生、发展提供科学依据.方法 间期双色荧光原位杂交(FISH)技术检测34例PTCL-NOS(其中19例经过a-CGH检测)中FGR和TP73的基因改变,所用探针为缺口平移法自制的FGR和TP73特异位点探针以及商品化1号染色体着丝粒探针(CEP1).结果 34例中出现基因改变者7例(20.6%),其中FGR扩增1例,TP73扩增2例;FGR和TP73同时出现基因改变4例(11.8%),其中同时杂合性缺失(LOH)1例,同时扩增3例.CEP1扩增4例(11.8%),与TP73/FGR基因扩增同时存在.Kaplan-Meier生存分析显示基因改变组较基因无改变组以及TP73改变组较TP73无改变组均有预后不良的趋势,但差异无统计学意义(均P>0.05).结论 FISH结果部分验证了前期a-CGH的研究发现;淋巴瘤相关基因FGR和TP73改变以及1号染色体多倍体可能在PTCL-NOS的发生、发展中起着重要的作用.

Genetic aberration of FGR and TP73 in peripheral T cell lymphoma not otherwise specified

Objective To investigate the genetic changes of FGR and TP73 in PTCL-NOS, in order to verify the results of our previous a-CGH study and to explore their role on the pathogenesis of PTCL-NOS. Methods A total of 34 cases, of which 19 cases were examined by a-CGH, were investigated by interphasedual-colour FISH using homemade site-specific probes of FGR and TP73 by using a labelling method of nick translation and commercial probe CEP1. Results In general, 7 of 34 (20.6 %) cases of PTCL-NOS showed genetic aberrations, of which 4 cases had changes on both of the loci of FGR and TP73, including 3 cases of amplification and 1 loss of heterozygosity (LOH), 1 case of FGR amplification and other 2 TP73 amplification only. CEP1 amplification was detected in 4 cases (11.8 %), simultaneously associated with FGR/ TP73 gene amplification. Kaplan-Meier survival analysis indicated there was a trend that the group with genetic changes had a poorer prognosis than the group of non-genetic changes, and so as the group of TP73 genetic changes compared with the group of TP73 non-genetic changes, although their was no statistical significance (P >0.05). Conclusion The outcome of this study partially verified the results of a-CGH, and aberration of lymphoma-related genes FGR and TP73, and the amplification of CEP1 may play a significant role in the pathogenesis of PTCL-NOS.