Jin Yaqiong, Wang Huanmin, Han Wei, Lu Jie, Chu Ping, Han Shujing, Ni Xin, Ning Baitang, Yu Dianke, Guo Yongli
Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Tumour Biol. 2016 Mar;37(3):3739-47. doi: 10.1007/s13277-015-4192-6. Epub 2015 Oct 14.
With a primary mortality, neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Amplification of the MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog) oncogene is observed in 20-30 % of NB cases, a feature which also characterizes a highly aggressive subtype of the disease. However, the systematic study of association between single nucleotide polymorphisms (SNPs) in MYCN-regulated genes and the risk of NB has not been investigated. In the current study, we scanned a set of 16 SNPs located within known or predicted MYCN binding sites in a cohort of 247 patients of Chinese origin with neuroblastic family tumors, including neuroblastoma (NB), ganglioneuroma (GN), and ganglioneuroblastoma (GNB), and in 290 cancer-free controls to determine whether any of the tested SNPs are associated with neuroblastic family tumors. We found that the rs11669203 G>C polymorphism, located in TGFBR3L promoter, is significantly associated with the risk of NB. Further, we found that this association is site specific to adrenal NB compared to non-adrenal NB. In addition, transcriptome analysis indicated that increased expression of TGFBR3L is strongly correlated with poor survival. The SNP rs11669203 located at the MYCN binding site of TGFBR3L is significantly associated with elevated risk of NB, and abnormal MYCN-regulated TGFBR3L expression may contribute to NB oncogenesis.
作为主要死因，神经母细胞瘤（NB）是儿童期最常见的颅外实体瘤。在20%-30%的NB病例中观察到MYCN（v-myc禽骨髓细胞瘤病毒癌基因神经母细胞瘤衍生同源物）癌基因的扩增，这一特征也表征了该疾病的一种高度侵袭性亚型。然而，尚未对MYCN调控基因中的单核苷酸多态性（SNP）与NB风险之间的关联进行系统研究。在本研究中，我们扫描了一组位于已知或预测的MYCN结合位点内的16个SNP，这些位点来自247例患有神经母细胞瘤家族肿瘤（包括神经母细胞瘤（NB）、神经节瘤（GN）和神经节神经母细胞瘤（GNB））的中国患者队列以及290例无癌对照，以确定任何测试的SNP是否与神经母细胞瘤家族肿瘤相关。我们发现位于TGFBR3L启动子中的rs11669203 G>C多态性与NB风险显著相关。此外，我们发现这种关联在肾上腺NB中具有位点特异性，与非肾上腺NB相比。此外，转录组分析表明TGFBR3L表达增加与较差的生存率密切相关。位于TGFBR3L的MYCN结合位点的SNP rs11669203与NB风险升高显著相关，并且异常的MYCN调控的TGFBR3L表达可能有助于NB的发生。
