Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
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DOI：
10.1038/nature11327
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发表时间：
2012-08-02
期刊：
影响因子：
64.8
通讯作者：
Taylor MD
中科院分区：
文献类型：
--
作者：
Northcott PA;Shih DJ;Peacock J;Garzia L;Morrissy AS;Zichner T;Stütz AM;Korshunov A;Reimand J;Schumacher SE;Beroukhim R;Ellison DW;Marshall CR;Lionel AC;Mack S;Dubuc A;Yao Y;Ramaswamy V;Luu B;Rolider A;Cavalli FM;Wang X;Remke M;Wu X;Chiu RY;Chu A;Chuah E;Corbett RD;Hoad GR;Jackman SD;Li Y;Lo A;Mungall KL;Nip KM;Qian JQ;Raymond AG;Thiessen NT;Varhol RJ;Birol I;Moore RA;Mungall AJ;Holt R;Kawauchi D;Roussel MF;Kool M;Jones DT;Witt H;Fernandez-L A;Kenney AM;Wechsler-Reya RJ;Dirks P;Aviv T;Grajkowska WA;Perek-Polnik M;Haberler CC;Delattre O;Reynaud SS;Doz FF;Pernet-Fattet SS;Cho BK;Kim SK;Wang KC;Scheurlen W;Eberhart CG;Fèvre-Montange M;Jouvet A;Pollack IF;Fan X;Muraszko KM;Gillespie GY;Di Rocco C;Massimi L;Michiels EM;Kloosterhof NK;French PJ;Kros JM;Olson JM;Ellenbogen RG;Zitterbart K;Kren L;Thompson RC;Cooper MK;Lach B;McLendon RE;Bigner DD;Fontebasso A;Albrecht S;Jabado N;Lindsey JC;Bailey S;Gupta N;Weiss WA;Bognár L;Klekner A;Van Meter TE;Kumabe T;Tominaga T;Elbabaa SK;Leonard JR;Rubin JB;Liau LM;Van Meir EG;Fouladi M;Nakamura H;Cinalli G;Garami M;Hauser P;Saad AG;Iolascon A;Jung S;Carlotti CG;Vibhakar R;Ra YS;Robinson S;Zollo M;Faria CC;Chan JA;Levy ML;Sorensen PH;Meyerson M;Pomeroy SL;Cho YJ;Bader GD;Tabori U;Hawkins CE;Bouffet E;Scherer SW;Rutka JT;Malkin D;Clifford SC;Jones SJ;Korbel JO;Pfister SM;Marra MA;Taylor MD
髓母细胞瘤是最常见的儿童恶性脑肿瘤，目前采用非特异性细胞毒性疗法治疗，包括手术、全脑放疗和积极化疗。由于髓母细胞瘤表现出明显的肿瘤间异质性，至少有四种不同的分子变异体，以前的尝试，以确定治疗的目标已经不足，由于样本量小。在这里，我们报告体细胞拷贝数畸变（SCNAs）在1087独特的髓母细胞瘤。SCNA在髓母细胞瘤中很常见，并且主要是亚群富集。局灶性拷贝数增加的最常见区域是帕金森病基因SNCAIP的串联重复，其精确地限制于第4α组。PVT 1的反复易位，包括PVT 1-MYC和PVT 1-NDRG 1，通过chromothripsis产生，仅限于第3组。许多靶向SCNA，包括第3组中靶向TGFβ信号传导和第4组中靶向NF-κB信号传导的复发事件，提示了未来合理靶向治疗的途径。
Medulloblastoma, the most common malignant pediatric brain tumour, is currently treated with non-specific cytotoxic therapies including surgery, whole brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, prior attempts to identify targets for therapy have been underpowered due to small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup enriched. The most common region of focal copy number gain is a tandem duplication of the Parkinson’s disease gene SNCAIP, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1 that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGFβ signaling in Group 3, and NF-κB signaling in Group 4 suggest future avenues for rational, targeted therapy.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Parks, WT;Frank, DB;Lechleider, RJ
通讯作者：
Lechleider, RJ
影响因子：
12.7
作者：
Northcott PA;Hielscher T;Dubuc A;Mack S;Shih D;Remke M;Al-Halabi H;Albrecht S;Jabado N;Eberhart CG;Grajkowska W;Weiss WA;Clifford SC;Bouffet E;Rutka JT;Korshunov A;Pfister S;Taylor MD
通讯作者：
Taylor MD
DOI：
10.1126/science.1198056
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Li M;Zhang X;Jones S;Leary RJ;Lin JC;Boca SM;Carter H;Samayoa J;Bettegowda C;Gallia GL;Jallo GI;Binder ZA;Nikolsky Y;Hartigan J;Smith DR;Gerhard DS;Fults DW;VandenBerg S;Berger MS;Marie SK;Shinjo SM;Clara C;Phillips PC;Minturn JE;Biegel JA;Judkins AR;Resnick AC;Storm PB;Curran T;He Y;Rasheed BA;Friedman HS;Keir ST;McLendon R;Northcott PA;Taylor MD;Burger PC;Riggins GJ;Karchin R;Parmigiani G;Bigner DD;Yan H;Papadopoulos N;Vogelstein B;Kinzler KW;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
11.2
作者：
Adamson DC;Shi Q;Wortham M;Northcott PA;Di C;Duncan CG;Li J;McLendon RE;Bigner DD;Taylor MD;Yan H
通讯作者：
Yan H