Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.
Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.
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DOI：
10.1016/j.ccr.2014.02.004
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发表时间：
2014-03-17
期刊：
影响因子：
50.3
通讯作者：
ICGC PedBrain Tumor Project
中科院分区：
文献类型：
--
作者：
Kool M;Jones DT;Jäger N;Northcott PA;Pugh TJ;Hovestadt V;Piro RM;Esparza LA;Markant SL;Remke M;Milde T;Bourdeaut F;Ryzhova M;Sturm D;Pfaff E;Stark S;Hutter S;Seker-Cin H;Johann P;Bender S;Schmidt C;Rausch T;Shih D;Reimand J;Sieber L;Wittmann A;Linke L;Witt H;Weber UD;Zapatka M;König R;Beroukhim R;Bergthold G;van Sluis P;Volckmann R;Koster J;Versteeg R;Schmidt S;Wolf S;Lawerenz C;Bartholomae CC;von Kalle C;Unterberg A;Herold-Mende C;Hofer S;Kulozik AE;von Deimling A;Scheurlen W;Felsberg J;Reifenberger G;Hasselblatt M;Crawford JR;Grant GA;Jabado N;Perry A;Cowdrey C;Croul S;Zadeh G;Korbel JO;Doz F;Delattre O;Bader GD;McCabe MG;Collins VP;Kieran MW;Cho YJ;Pomeroy SL;Witt O;Brors B;Taylor MD;Schüller U;Korshunov A;Eils R;Wechsler-Reya RJ;Lichter P;Pfister SM;ICGC PedBrain Tumor Project
平滑(SMO)抑制剂最近进入了治疗声波刺猬驱动的髓母细胞瘤(SHH-MB)的临床试验。临床反应是高度可变的。为了了解原发性耐药的机制(S)，并确定与SHH信号异常协同的通路，我们对大量SHH-MBS(n=133)进行了测序和分析。Shh途径突变涉及ptch1(所有年龄段)、SUFU(婴儿，包括生殖系)和SMO(成人)。3岁的儿童携带过多的MYCN和GLI2下游扩增片段和频繁的TP53突变，通常发生在生殖系中，所有这些在婴儿和成人中都是罕见的。在不同的SHH-MB异种移植模型中的功能分析表明，携带ptch1突变的SHH-MB对SMO抑制有反应，而携带SUFU突变或MYCN扩增的肿瘤则主要耐药。
Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.
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影响因子：
12.7
作者：
Grammel, Daniel;Warmuth-Metz, Monika;Schueller, Ulrich
通讯作者：
Schueller, Ulrich
影响因子：
64.8
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
通讯作者：
Taylor MD
DOI：
10.1016/j.ijrobp.2006.12.030
发表时间：
2007-06-01
影响因子：
7
作者：
Padovani, Laetitia;Sunyach, Marie-Pierre;Carrie, Christian
通讯作者：
Carrie, Christian
影响因子：
45.3
作者：
Low, Jennifer A.;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
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