儿童神经母细胞瘤中ALK基因突变的研究

杨春兰,岳丽杰,江贤萍,文飞球,郑苗苗

中国当代儿科杂志 ›› 2012, Vol. 14 ›› Issue (10) : 763-766.

PDF(1141 KB)
PDF(1141 KB)
中国当代儿科杂志 ›› 2012, Vol. 14 ›› Issue (10) : 763-766.
论著·临床研究

儿童神经母细胞瘤中ALK基因突变的研究

  • 杨春兰,岳丽杰,江贤萍,文飞球,郑苗苗
作者信息 +

ALK gene mutations in childhood neuroblastoma

  • YANG Chun-Lan, YUE Li-Jie, JIANG Xian-Ping, WEN Fei-Qiu, ZHENG Miao-Miao
Author information +
文章历史 +

摘要

目的:探讨中国儿童神经母细胞瘤(NB)中间变性淋巴瘤激酶(ALK)基因的突变情况。方法:从22例石蜡包埋的NB肿瘤组织中提取基因组DNA,通过PCR-DNA直接测序技术分析儿童NB肿瘤组织中ALK突变热点区域第20~26号外显子的突变情况。结果:22 例儿童NB中,有10例(46%)在ALK第21号外显子上存在已知同义突变C3375A(Gly1125Gly),等位基因频率为27%;1例(5%)在ALK第23号外显子上发现一个新的同义突变C3586T(Leu1196Leu)。ALK突变C3375A的发生频率在NB患儿的年龄、性别、肿瘤分化程度和是否转移方面差异无统计学意义(P>0.05)。在其他5个ALK外显子中未发现突变。结论:采用PCR-DNA测序技术发现了ALK一个新的同义突变C3586T,并证实了儿童ALK存在已知突变C3375A,其发生率不受NB患儿临床特征的影响。

Abstract

OBJECTIVE: To investigate mutations of anaplastic lymphoma kinase (ALK) in Chinese children with neuroblastoma (NB). METHODS: Genomic DNA was extracted from 22 cases of paraffin-embedding NB tumor tissues. Gene mutations in the exons 20-26 which were mutational hotspots of ALK were analyzed by PCR-DNA direct sequencing. RESULTS: A novel synonymous mutation C3586T (Leu1196Leu) and a known synonymous mutation C3375A (Gly1125Gly) were found and located at exon 23 and exon 21 of ALK respectively. There were 10 cases (46%) of known synonymous mutation C3375A in 22 cases of NB. The C3375A allelic frequency was 27%. No statistically significant correlation was found between mutation C3375A and clinical parameters of NB such as age, sex, metastasis and tumor differentiation. Mutation was not found in the other 5 exons. CONCLUSIONS: A novel ALK gene synonymous mutation C3586T was identified using PCR-DNA sequencing. A known mutation C3375A in ALK was successfully identified in children, and its incidence is not influenced by the clinical features of childhood NB.

关键词

神经母细胞瘤 / 间变性淋巴瘤激酶 / 基因突变 / 儿童

Key words

Neuroblastoma / Anaplastic lymphoma kinase / Gene mutation / Child

引用本文

导出引用
杨春兰,岳丽杰,江贤萍,文飞球,郑苗苗. 儿童神经母细胞瘤中ALK基因突变的研究[J]. 中国当代儿科杂志. 2012, 14(10): 763-766
YANG Chun-Lan, YUE Li-Jie, JIANG Xian-Ping, WEN Fei-Qiu, ZHENG Miao-Miao. ALK gene mutations in childhood neuroblastoma[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(10): 763-766
中图分类号: R730.264   

参考文献

[1]杨春兰,岳丽杰.间变性淋巴瘤激酶与神经母细胞瘤关系的研究进展[J].中国肿瘤临床,2012,39(11):813-816.

[2]朱琪琦,刘英,冯晨,唐锁勤. 神经母细胞瘤远期复发临床研究[J].中国当代儿科杂志,2010,12(12):995-997.

[3]Azarova AM, Gautam G, George RE. Emerging importance of ALK in neuroblastoma[J]. Semin Cancer Biol, 2011, 21(4): 267-275.

[4]Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, et al. Oncogenic mutations of ALK kinase in neuroblastoma[J]. Nature, 2008, 455(7215): 971-974.

[5]George RE, Sanda T, Hanna M, Fr-hling S, Luther W 2nd, Zhang J, et al. Activating mutations in ALK provide a therapeutic target in neuroblastom[J]. Nature, 2008, 455(7215): 975-978.

[6]Carén H, Abel F, Kogner P, Martinsson T. High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumors[J]. Biochem J, 2008, 416(2): 153-159.

[7]张锦华,王维林,陈鸿骏.小儿神经母细胞瘤[M].北京:人民卫生出版社,2009:89-92.

[8]Li R, Morris SW. Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy[J]. Med Res Rev, 2008, 28(3): 372-412.

[9]Pearson R, Kolesar JM. Targeted therapy for NSCLC: ALK inhibition[J]. J Oncol Pharm Pract, 2012, 18(2): 271-274.

[10]Janoueix-Lerosey I, Lequin D, Brugières L, Ribeiro A, de Pontual L, Combaret V, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma[J]. Nature, 2008, 455(7215): 967-970.

[11]Mossé YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, et al. Identification of ALK as a major familial neuroblastoma predisposition gene[J]. Nature, 2008, 455(7215): 930-935.

[12]Kwon MJ, Choi YL, Sung KW, Kang SY, Park SM, Choi SY, et al. Oncogenic anaplastic lymphoma kinase (ALK) mutation in neuroblastomas and other pediatric tumors[J]. PatholRes Pract, 2011,  207(10): 634-639.

[13]Bagci O, Tumer S, Olgun N, Altungoz O. Copy number status and mutation analyses of anaplastic lymphoma kinase (ALK) gene in 90 sporadic neuroblastoma tumors[J]. Cancer Lett, 2012, 317(1): 72-77.

[14]Passoni L, Longo L, Collini P, Coluccia AM, Bozzi F, Podda M, et al. Mutation-independent anaplastic lymphoma kinase overexpression in poor prognosis neuroblastoma patients[J]. Cancer Res, 2009, 69(18): 7338-7346.

PDF(1141 KB)

Accesses

Citation

Detail

段落导航
相关文章

/