2012年12月3日 訊 /生物谷BIOON/ --近日,，來(lái)自約翰霍普金斯基墨爾癌癥中心等處的研究者通過(guò)對(duì)74個(gè)患有神經(jīng)細(xì)胞瘤的兒童進(jìn)行研究，發(fā)現(xiàn)這些患者機(jī)體中存在兩個(gè)基因：ARID1A和ARID1B的改變,，相比沒(méi)有這兩個(gè)基因改變的個(gè)體來(lái)講,，患病個(gè)體的生存時(shí)間僅僅是前者的四分之一。這項(xiàng)研究發(fā)現(xiàn)有助于幫助研究者開(kāi)發(fā)出早期的神經(jīng)細(xì)胞瘤鑒定方法及療法,。相關(guān)研究成果刊登于國(guó)際雜志Nature Genetics上,。
神經(jīng)細(xì)胞瘤可以影響全身的神經(jīng)組織，是常見(jiàn)的兒童非血液型癌癥,。這項(xiàng)研究中,，研究者分析了74個(gè)患者,，發(fā)現(xiàn)其中71名個(gè)體都存在機(jī)體堿基對(duì)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(xì)胞瘤相關(guān),，包括ALK和MYCN基因的突變。71個(gè)患病個(gè)體中有8人,，其存在基因ARID1A和ARID1B的改變,，這兩個(gè)基因控制DNA折疊的方式，進(jìn)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(shí)研究者檢測(cè)了并且監(jiān)控了四組父母其血液中神經(jīng)細(xì)胞瘤特異性的基因改變，并且將這些發(fā)現(xiàn)與疾病進(jìn)展進(jìn)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(guò)手術(shù)治療之后機(jī)體中還存在殘留的癌癥細(xì)胞。
下一步研究者計(jì)劃進(jìn)行深入研究,，研究者希望對(duì)更多的人群進(jìn)行研究來(lái)確定ARID1A和ARID1B這兩個(gè)基因是否和疾病的預(yù)測(cè)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.
