来自约翰霍普金斯大学Kimmel癌症中心和费城儿童医院的科学家们在对74个儿童神经母细胞瘤进行全基因组测序后，发现ARID1A和ARID1B两个基因发生改变的患儿相比无此基因改变的患儿生存期缩短3/4。这一发现有可能最终导致早期确认患有侵袭性神经母细胞瘤的儿童，他们或许需要接受其他的治疗。相关论文发表在《自然遗传学》(Nature Genetics)杂志上。
在本研究的74个肿瘤中，有71个进行了重排和碱基对改变分析。研究人员找到了与神经母细胞瘤有关联的多个基因，包括ALK和MYCN基因中发现了癌症特异性的突变。他们还发现71名患者中8人有ARID1A和ARID1B基因的改变，这两个基因通常情况下通过调控DNA折叠方式来影响蛋白质合成。
科学家们还检测和监控了4名患者血液中神经母细胞瘤特异性的遗传改变，并确定了这些研究结果与疾病进程之间的相互关联。
Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma
Mark Sausen, Rebecca J Leary, Siân Jones, Jian Wu, C Patrick Reynolds, Xueyuan Liu, Amanda Blackford, Giovanni Parmigiani, Luis A Diaz Jr, Nickolas Papadopoulos, Bert Vogelstein, Kenneth W Kinzler, Victor E Velculescu & Michael D Hogarty
Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma, we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases) and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average, each tumor had 19 somatic alterations in coding genes (range of 3–70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of the chromatin-remodeling genes ARID1A and ARID1B were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight the dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of patients with neuroblastoma.
