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.
［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.
