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Single nucleotide polymorphism rs11669203 in TGFBR3L is associated with the risk of neuroblastoma in a Chinese population

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Tumor Biology

Abstract

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.

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Funding

Supported by National Natural Science Foundation of China (81472369) and Clinical Research Special Foundation by Wu Jieping Medical Foundation (320. 6750. 12398).

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    Authors and Affiliations

    1. 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

      Yaqiong Jin, Jie Lu, Ping Chu, Shujing Han, Xin Ni & Yongli Guo

    2. Department of Surgical Oncology, Beijing Children’s Hospital, Capital Medical University, Beijing, China

      Huanmin Wang & Wei Han

    3. Department of Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, Beijing, China

      Xin Ni

    4. National Center for Toxicological Research, US Food and Drug Administration, Jefferson, USA

      Baitang Ning & Dianke Yu

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    Correspondence to Dianke Yu or Yongli Guo.

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    Yaqiong Jin and Huanmin Wang contributed equally to this work.

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    Jin, Y., Wang, H., Han, W. et al. Single nucleotide polymorphism rs11669203 in TGFBR3L is associated with the risk of neuroblastoma in a Chinese population. Tumor Biol. 37, 3739–3747 (2016). https://doi.org/10.1007/s13277-015-4192-6

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