2012年12月3日 讯 /生物谷BIOON/ --近日,来自约翰霍普金斯基墨尔癌症中心等处的研究者通过对74个患有神经细胞瘤的儿童进行研究,发现这些患者机体中存在两个基因:ARID1A和ARID1B的改变,相比没有这两个基因改变的个体来讲,患病个体的生存时间仅仅是前者的四分之一。这项研究发现有助于帮助研究者开发出早期的神经细胞瘤鉴定方法及疗法。相关研究成果刊登于国际杂志Nature Genetics上。
神经细胞瘤可以影响全身的神经组织,是常见的儿童非血液型癌症。这项研究中,研究者分析了74个患者,发现其中71名个体都存在机体碱基对重排和改变的情况,此前发现,癌症特异性的基因突变和神经细胞瘤相关,包括ALK和MYCN基因的突变。71个患病个体中有8人,其存在基因ARID1A和ARID1B的改变,这两个基因控制DNA折叠的方式,进而影响蛋白质的产生。
携带有ARID1A和ARID1B基因改变的儿童表现出低的生存率,于此同时研究者检测了并且监控了四组父母其血液中神经细胞瘤特异性的基因改变,并且将这些发现与疾病进展进行关联。
研究血液中癌症特异性基因的改变可以帮助医生监控那些疾病复发的患者,并且帮助医生决定是否患者经过手术治疗之后机体中还存在残留的癌症细胞。
下一步研究者计划进行深入研究,研究者希望对更多的人群进行研究来确定ARID1A和ARID1B这两个基因是否和疾病的预测直接相关,相关研究由St. Baldrick等基金提供资助。(生物谷Bioon.com)
doi:10.1038/ng.2493
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Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma
Mark Sausen,1, 10 Rebecca J Leary,1, 10 Siân Jones,1, 9 Jian Wu,1, 9 C Patrick Reynolds,2 Xueyuan Liu,3 Amanda Blackford,4 Giovanni Parmigiani,5, 6 Luis A Diaz Jr,1 Nickolas Papadopoulos,1 Bert Vogelstein,1, 7 Kenneth W Kinzler,1 Victor E Velculescu1 & Michael D Hogarty3, 8
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.