Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Sci Rep. 2017 Dec 19;7(1):17787. doi: 10.1038/s41598-017-17162-y.
Neuroblastoma is a pediatric tumor characterized by histologic heterogeneity, and accounts for ~15% of childhood deaths from cancer. The five-year survival for patients with high-risk stage 4 disease has not improved in two decades. We used whole exome sequencing (WES) to identify mutations present in three independent high-risk stage 4 neuroblastoma tumors (COA/UAB-3, COA/UAB -6 and COA/UAB -8) and a stage 3 tumor (COA/UAB-14). Among the four tumors WES analysis identified forty-three mutations that had not been reported previously, one of which was present in two of the four tumors. WES analysis also corroborated twenty-two mutations that were reported previously. No single mutation occurred in all four tumors or in all stage 4 tumors. Three of the four tumors harbored genes with CADD scores ≥20, indicative of mutations associated with human pathologies. The average depth of coverage ranged from 39.68 to 90.27, with >99% sequences mapping to the genome. In summary, WES identified sixty-five coding mutations including forty-three mutations not reported previously in primary neuroblastoma tumors. The three stage 4 tumors contained mutations in genes encoding protein products that regulate immune function or cell adhesion and tumor cell metastasis.
神经母细胞瘤是一种儿科肿瘤，具有组织学异质性，约占儿童癌症死亡人数的 15%。患有高危 4 期疾病的患者的五年生存率在过去二十年中没有改善。我们使用全外显子组测序（WES）来鉴定三个独立的高危 4 期神经母细胞瘤肿瘤（COA/UAB-3、COA/UAB-6 和 COA/UAB-8）和一个 3 期肿瘤（COA/UAB-14）中存在的突变。在 WES 分析鉴定的四十三个以前未报道过的突变中，有一个存在于四个肿瘤中的两个。WES 分析还证实了以前报道过的二十个突变。没有一个突变发生在所有四个肿瘤或所有 4 期肿瘤中。四个肿瘤中有三个携带有 CADD 评分≥20 的基因，表明存在与人类病理相关的突变。平均覆盖深度范围从 39.68 到 90.27，有超过 99%的序列映射到基因组。总之，WES 鉴定了 65 个编码突变，包括以前在原发性神经母细胞瘤肿瘤中未报道过的 43 个突变。三个 4 期肿瘤中存在编码调节免疫功能或细胞黏附以及肿瘤细胞转移的蛋白产物的基因突变。
