儿童神经母细胞源性肿瘤中N-myc和C-myc基因的分子遗传学异常及其临床病理学意义  

Molecular genetic abnormalities of N-myc and C-myc in pediatric neuroblastic tumors and clinicalpathologic significance

作　　者：蔡荣芹[1] 周春菊[2] 孙勤暖[3] 马晓莉[4] 王苗[1] 李勇[1] 王大业[1] 宫丽平[1] 

机构地区：[1]首都医科大学病理学系,100069 [2]首都医科大学附属北京儿童医院病理科 [3]内蒙古医学院病理学系 [4]首都医科大学附属北京儿童医院血液科

出　　处：《中华病理学杂志》2013年第5期299-304,共6页Chinese Journal of Pathology

基　　金：北京市自然科学基金（7122025）;北京优秀人才资助项目（2011D005018000008）

摘　　要：目的研究儿童神经母细胞源性肿瘤（NT）中N-myc和C-myc基因的分子遗传学异常及其临床病理学意义。方法应用问期荧光原位杂交（FISH）技术检测246例NT标本[神经母细胞瘤（NB）188例，节细胞神经母细胞瘤（GNB）52例，节细胞神经瘤（GN）6例]中N-myc异常，并与组织学类型、预后进行相关性分析，同时对其中的133例NT进行C-myc基因的FISH检测。结果246例NT中，N-myc总扩增率为11．0％（27／246），所有扩增均发生在NB中，52例GNB及6例GN中无1例存在N-myc扩增（P〈0．05）。246例NT中，N-myc非扩增者占89．0％（219／246），包括N-myc的获得者（71．1％，175／246）和正常者（17．9％，44／246）。单因素生存分析显示，N-myc扩增者预后比N-myc非扩增者差（P=0．012）；N-myc非扩增者中，N-myc获得者预后与N-myc正常者相比，差异无显著统计学意义（P=0．057）。进行C-myc检测的133例NT中，55．6％（74／133）存在C-myc的获得，未见C-myc扩增及易位者。6／15N—myc扩增者与57．6％（68／118）N-myc非扩增者，伴C-myc获得，两者的差异无统计学意义（P〉0．05）。C-myc基因的单因素生存分析显示，C-myc获得者预后与C-myc正常者相比，差异无统计学意义（P=0．357）。结论我国儿童NT中N-myc扩增率较低，且仅存在于NB中；N-myc扩增者预后差；儿童NT中未检测到C-myc的扩增及易位，但C—myc获得较常见；N-myc扩增与C-myc获得之间无明显相关性。Objective To investigate the molecular genetic abnormalities of N-myc and C-myc, and their clinical pathological implications in pediatric neuroblastic tumors （ NTs ）. Methods Abnormalities of N-myc were detected by interphase fluorescence in situ hybridization （FISH） technique in 246 cases of NTs, including neuroblastoma （ NB, 188 cases） , ganglioneuroblastoma （ GNB,52 cases） , ganglioneuroma （ GN, 6 cases） , and their association with the histological typing of the tumors and prognosis was analyzed. Abnormalities of C-myc were detected by FISH in 133 cases of NTs. Results Of the 246 cases of NTs, N-myc amplification was only found in 27 cases （ 11.0% , 27/246） of NB, but not in any cases of GNB or GN （P 〈 0. 05 ）. 89. 0% （219/246） N-mye non-amplification were found in NTs, and it included N-myc gain in 175 cases （71.1%, 175/246）and normal N-myc in 44 cases （17.9%, 44/246）. Univariate analysis indicated significantly （P = 0. 012） poorer outcome in patients with N-myc amplification than N-myc non-amplification. However no significant difference was observed between N-myc gain cases and normal N-myc cases （P = 0.057）. C-myc gain was found in 74 of 133 cases （55.6%） of NTs; no C-myc amplification or transloeation was detected. Forty percent （6/15） of eases with N-mye amplification and57.6% （68/118） of cases with N-myc non-amplification were accompanied by C-myc gain. The difference between N-myc amplification and non-amplification with C-myc gain was not significant （ P 〉 0. 05 ） . Univariate analysis indicated that the outcome difference was not statistically significant between C-myc gain cases and normal C-myc eases （P = 0. 357）. Conclusions The incidence of N-myc amplification only found in NB is low in pediatric NTs in China. Patients with N-myc amplification predict poorer outcome. No amplification or transloeation of C-myc is detected in NTs, whereas C-myc gain is relatively common in NTs. There is no obvious association between N-myc am

关 键 词：神经母细胞瘤 基因 myc 原位杂交 荧光 预后 

分 类 号：R73[医药卫生—肿瘤]