2012年12月3日 訊 /生物谷BIOON/ --近日，來自約翰霍普金斯基墨爾癌癥中心等處的研究者通過對74個患有神經(jīng)細胞瘤的兒童進行研究，發(fā)現(xiàn)這些患者機體中存在兩個基因：ARID1A和ARID1B的改變，相比沒有這兩個基因改變的個體來講，患病個體的生存時間僅僅是前者的四分之一,。這項研究發(fā)現(xiàn)有助于幫助研究者開發(fā)出早期的神經(jīng)細胞瘤鑒定方法及療法。相關(guān)研究成果刊登于國際雜志Nature Genetics上,。
神經(jīng)細胞瘤可以影響全身的神經(jīng)組織,，是常見的兒童非血液型癌癥。這項研究中,，研究者分析了74個患者,，發(fā)現(xiàn)其中71名個體都存在機體堿基對重排和改變的情況，此前發(fā)現(xiàn),，癌癥特異性的基因突變和神經(jīng)細胞瘤相關(guān),，包括ALK和MYCN基因的突變。71個患病個體中有8人,，其存在基因ARID1A和ARID1B的改變,，這兩個基因控制DNA折疊的方式，進而影響蛋白質(zhì)的產(chǎn)生,。
攜帶有ARID1A和ARID1B基因改變的兒童表現(xiàn)出低的生存率,，于此同時研究者檢測了并且監(jiān)控了四組父母其血液中神經(jīng)細胞瘤特異性的基因改變，并且將這些發(fā)現(xiàn)與疾病進展進行關(guān)聯(lián),。
研究血液中癌癥特異性基因的改變可以幫助醫(yī)生監(jiān)控那些疾病復(fù)發(fā)的患者,，并且?guī)椭t(yī)生決定是否患者經(jīng)過手術(shù)治療之后機體中還存在殘留的癌癥細胞。
下一步研究者計劃進行深入研究,，研究者希望對更多的人群進行研究來確定ARID1A和ARID1B這兩個基因是否和疾病的預(yù)測直接相關(guān),，相關(guān)研究由St. Baldrick等基金提供資助。（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.
