Department of Oncology,Bishan Hospital of Chongqing Medical University, The People's Hospital of Bishan District, Chongqing, China.
Department of Otolaryngology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Cancer Control. 2023 Jan-Dec;30:10732748231175017. doi: 10.1177/10732748231175017.
Neuroblastoma (NB) is one of the children's most common solid tumors, accounting for approximately 8% of pediatric malignancies and 15% of childhood cancer deaths. Somatic mutations in several genes, such as , have been associated with NB progression and can facilitate the discovery of novel therapeutic strategies. However, the differential expression of mutated and wild-type alleles on the transcriptome level is poorly studied.
This study analyzed 219 whole-exome sequencing datasets with somatic mutations detected by MuTect from paired normal and tumor samples.
We prioritized mutations in 8 candidate genes (, , , , , , , and ) as potential driver mutations. We further confirmed the presence of allele-specific expression of the somatic mutations in NB with integrated analysis of 127 RNA-seq samples (of which 85 also had DNA-seq data available), including , , and . The allele-specific expression of mutations suggests that the same somatic mutation may have different effects on the clinical outcomes of tumors.
Our study suggests 2 novel variants of as a novel candidate driver gene for NB.
神经母细胞瘤（NB）是儿童最常见的实体肿瘤之一，约占儿童恶性肿瘤的 8%，占儿童癌症死亡人数的 15%。一些基因（如 ）中的体细胞突变与 NB 的进展有关，并有助于发现新的治疗策略。然而，在转录组水平上，突变型和野生型等位基因的差异表达研究甚少。
本研究分析了 219 个全外显子测序数据集，这些数据集来自配对的正常和肿瘤样本，通过 MuTect 检测到体细胞突变。
我们将 8 个候选基因（、、、、、、和 ）中的突变作为潜在的驱动突变进行了优先级排序。我们通过对 127 个 RNA-seq 样本（其中 85 个样本也有 DNA-seq 数据）的综合分析，进一步证实了 NB 中体细胞突变的等位基因特异性表达，包括 、 和 。突变的等位基因特异性表达表明，同一体细胞突变可能对肿瘤的临床结局有不同的影响。
我们的研究表明 2 个新的 变体可能是 NB 的一个新的候选驱动基因。
