Prognostic and radiographic correlates of a prospectively collected molecularly profiled cohort of IDH1/2-wildtype astrocytomas.
Prognostic and radiographic correlates of a prospectively collected molecularly profiled cohort of IDH1/2-wildtype astrocytomas.
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DOI：
10.1111/bpa.12826
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发表时间：
2020-05
期刊：
影响因子：
--
通讯作者：
Bale TA
中科院分区：
文献类型：
--
作者：
Lin AL;Rosenblum M;Mellinghoff IK;Tabar VS;Ogilvie S;Schaff L;Yang TJ;Young RJ;Taylor BS;Jonsson P;Bale TA
在分子时代，肿瘤分级与 IDH1/2 野生型 (WT) 胶质瘤预后的相关性一直存在争议。有人建议，具有胶质母细胞瘤 IDH1/2-WT 分子特征的组织学 II 级和 III 级星形细胞瘤与胶质母细胞瘤具有相似的预后，应考虑进行相同的临床试验。我们将 564 名 IDH1/2-WT 胶质瘤患者（26 名 II 级、71 名 III 级和 467 名 IV 级）的前瞻性临床测序与临床和放射学数据相结合，以评估分子特征、分级和结果之间的关联。与组织学 IV 级 IDH1/2-WT 星形细胞瘤相比，组织学 II 级星形细胞瘤具有较少的 7/10 染色体改变 (p=0.04)、EGFR 扩增 (p=0.022) 和细胞周期效应子改变 (p=1.9e-11)，但 TERT 启动子突变频率相似。相比之下，组织学 III 级和 IV 级 IDH1/2-WT 疾病中这些典型分子特征的频率没有差异。组织学 II 级肿瘤的无进展生存期 (PFS) 和总生存期 (OS) 显着长于 III 级肿瘤（分别为 p=0.02 和 p=0.008），而组织学 III 级肿瘤的 PFS 和 OS 与 IV 级肿瘤相比没有差异。组织学 II 级、III 级和 IV 级肿瘤的中位 PFS 分别为 19、11 和 9 个月。相同肿瘤的中位 OS 分别为 44、23 和 23 个月。在组织学 II 级和 III 级 IDH1/2 WT 肿瘤中，胶质瘤病与细胞周期改变的缺失相关 (p=0.008)，并且富含 II 级特征 (p=0.1) 和 PI3K-AKT 通路的改变 (p=0.09)。 II 级组织学与 IDH1/2-WT 星形细胞瘤的预后意义具有基因型和表型相关性。
In the molecular era, the relevance of tumor grade for prognostication of IDH1/2-wildtype (WT) gliomas has been debated. It has been suggested that histologic grade II and III astrocytomas with molecular features of glioblastoma, IDH1/2-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials. We integrated prospective clinical sequencing from 564 patients with IDH1/2-WT gliomas (26 grade II, 71 grade III, and 467 grade IV) with clinical and radiographic data to assess associations between molecular features, grade and outcome. Compared to histologic grade IV IDH1/2-WT astrocytomas, histologic grade II astrocytomas harbor fewer chromosome 7/10 alterations (p=0.04), EGFR amplifications (p=0.022), and alterations in cell-cycle effectors (p=1.9e-11), but a similar frequency of TERT promoter mutations. In contrast, there is no difference in the frequency of these canonical molecular features in histologic grade III versus IV IDH1/2-WT disease. Progression-free (PFS) and overall survival (OS) for histologic grade II tumors were significantly longer than grade III tumors (p=0.02 and p=0.008, respectively), whereas there was no difference in PFS and OS for histologic grade III compared to grade IV tumors. Median PFS for histologic grade II, III, and IV tumors was 19, 11, and 9 months, respectively. Median OS for the same tumors was 44, 23, and 23 months, respectively. In histologic grade II and III IDH1/2 WT tumors, gliomatosis is associated with the absence of cell-cycle alterations (p=0.008), and enriched in grade II features (p=0.1) and alterations in the PI3K-AKT pathway (p=0.09). Grade II histology has genotypic and phenotypic associations with prognostic implications in IDH1/2-WT astrocytomas.
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DOI：
10.1056/nejmoa1407279
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
通讯作者：
Jenkins RB
影响因子：
64.5
作者：
Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
通讯作者：
Hu H
影响因子：
28.2
作者：
Chang MT;Bhattarai TS;Schram AM;Bielski CM;Donoghue MTA;Jonsson P;Chakravarty D;Phillips S;Kandoth C;Penson A;Gorelick A;Shamu T;Patel S;Harris C;Gao J;Sumer SO;Kundra R;Razavi P;Li BT;Reales DN;Socci ND;Jayakumaran G;Zehir A;Benayed R;Arcila ME;Chandarlapaty S;Ladanyi M;Schultz N;Baselga J;Berger MF;Rosen N;Solit DB;Hyman DM;Taylor BS
通讯作者：
Taylor BS
DOI：
10.1056/nejmoa1402121
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cancer Genome Atlas Research Network;Brat DJ;Verhaak RG;Aldape KD;Yung WK;Salama SR;Cooper LA;Rheinbay E;Miller CR;Vitucci M;Morozova O;Robertson AG;Noushmehr H;Laird PW;Cherniack AD;Akbani R;Huse JT;Ciriello G;Poisson LM;Barnholtz-Sloan JS;Berger MS;Brennan C;Colen RR;Colman H;Flanders AE;Giannini C;Grifford M;Iavarone A;Jain R;Joseph I;Kim J;Kasaian K;Mikkelsen T;Murray BA;O'Neill BP;Pachter L;Parsons DW;Sougnez C;Sulman EP;Vandenberg SR;Van Meir EG;von Deimling A;Zhang H;Crain D;Lau K;Mallery D;Morris S;Paulauskis J;Penny R;Shelton T;Sherman M;Yena P;Black A;Bowen J;Dicostanzo K;Gastier-Foster J;Leraas KM;Lichtenberg TM;Pierson CR;Ramirez NC;Taylor C;Weaver S;Wise L;Zmuda E;Davidsen T;Demchok JA;Eley G;Ferguson ML;Hutter CM;Mills Shaw KR;Ozenberger BA;Sheth M;Sofia HJ;Tarnuzzer R;Wang Z;Yang L;Zenklusen JC;Ayala B;Baboud J;Chudamani S;Jensen MA;Liu J;Pihl T;Raman R;Wan Y;Wu Y;Ally A;Auman JT;Balasundaram M;Balu S;Baylin SB;Beroukhim R;Bootwalla MS;Bowlby R;Bristow CA;Brooks D;Butterfield Y;Carlsen R;Carter S;Chin L;Chu A;Chuah E;Cibulskis K;Clarke A;Coetzee SG;Dhalla N;Fennell T;Fisher S;Gabriel S;Getz G;Gibbs R;Guin R;Hadjipanayis A;Hayes DN;Hinoue T;Hoadley K;Holt RA;Hoyle AP;Jefferys SR;Jones S;Jones CD;Kucherlapati R;Lai PH;Lander E;Lee S;Lichtenstein L;Ma Y;Maglinte DT;Mahadeshwar HS;Marra MA;Mayo M;Meng S;Meyerson ML;Mieczkowski PA;Moore RA;Mose LE;Mungall AJ;Pantazi A;Parfenov M;Park PJ;Parker JS;Perou CM;Protopopov A;Ren X;Roach J;Sabedot TS;Schein J;Schumacher SE;Seidman JG;Seth S;Shen H;Simons JV;Sipahimalani P;Soloway MG;Song X;Sun H;Tabak B;Tam A;Tan D;Tang J;Thiessen N;Triche T Jr;Van Den Berg DJ;Veluvolu U;Waring S;Weisenberger DJ;Wilkerson MD;Wong T;Wu J;Xi L;Xu AW;Yang L;Zack TI;Zhang J;Aksoy BA;Arachchi H;Benz C;Bernard B;Carlin D;Cho J;DiCara D;Frazer S;Fuller GN;Gao J;Gehlenborg N;Haussler D;Heiman DI;Iype L;Jacobsen A;Ju Z;Katzman S;Kim H;Knijnenburg T;Kreisberg RB;Lawrence MS;Lee W;Leinonen K;Lin P;Ling S;Liu W;Liu Y;Liu Y;Lu Y;Mills G;Ng S;Noble MS;Paull E;Rao A;Reynolds S;Saksena G;Sanborn Z;Sander C;Schultz N;Senbabaoglu Y;Shen R;Shmulevich I;Sinha R;Stuart J;Sumer SO;Sun Y;Tasman N;Taylor BS;Voet D;Weinhold N;Weinstein JN;Yang D;Yoshihara K;Zheng S;Zhang W;Zou L;Abel T;Sadeghi S;Cohen ML;Eschbacher J;Hattab EM;Raghunathan A;Schniederjan MJ;Aziz D;Barnett G;Barrett W;Bigner DD;Boice L;Brewer C;Calatozzolo C;Campos B;Carlotti CG Jr;Chan TA;Cuppini L;Curley E;Cuzzubbo S;Devine K;DiMeco F;Duell R;Elder JB;Fehrenbach A;Finocchiaro G;Friedman W;Fulop J;Gardner J;Hermes B;Herold-Mende C;Jungk C;Kendler A;Lehman NL;Lipp E;Liu O;Mandt R;McGraw M;Mclendon R;McPherson C;Neder L;Nguyen P;Noss A;Nunziata R;Ostrom QT;Palmer C;Perin A;Pollo B;Potapov A;Potapova O;Rathmell WK;Rotin D;Scarpace L;Schilero C;Senecal K;Shimmel K;Shurkhay V;Sifri S;Singh R;Sloan AE;Smolenski K;Staugaitis SM;Steele R;Thorne L;Tirapelli DP;Unterberg A;Vallurupalli M;Wang Y;Warnick R;Williams F;Wolinsky Y;Bell S;Rosenberg M;Stewart C;Huang F;Grimsby JL;Radenbaugh AJ;Zhang J
通讯作者：
Zhang J
影响因子：
12.7
作者：
Hartmann, Christian;Hentschel, Bettina;von Deimling, Andreas
通讯作者：
von Deimling, Andreas