Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors

被引:131
作者
Patel, Akash J. [1 ,2 ]
Wan, Ying-Wooi [2 ,3 ]
Al-Ouran, Rami [2 ,4 ]
Revelli, Jean-Pierre [2 ,3 ]
Cardenas, Maria F. [5 ]
Oneissi, Mazen [1 ,2 ]
Xi, Liu [5 ]
Jalali, Ali [1 ]
Magnotti, John F. [1 ]
Muzny, Donna M. [5 ]
Doddapaneni, HarshaVardhan [5 ]
Sebastian, Sherly [1 ]
Heck, Kent A. [6 ]
Goodman, Clay [6 ]
Gopinath, Shankar P. [1 ]
Liu, Zhandong [2 ,4 ]
Rao, Ganesh [7 ]
Plon, Sharon E. [3 ,4 ]
Yoshor, Daniel [1 ,8 ]
Wheeler, David A. [5 ]
Zoghbi, Huda Y. [2 ,3 ,4 ,8 ,9 ]
Klisch, Tiemo J. [2 ,3 ]
机构
[1] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA
[2] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[4] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[5] Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA
[6] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
[7] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA
[8] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA
[9] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA
关键词
NF2; oncogenesis; brain tumor; classification; PRC2; GENOMIC ANALYSIS; CHROMOSOME; 1P; FREE SURVIVAL; EXPRESSION; MUTATIONS; CLASSIFICATION; SYSTEM; EZH1; AKT1;
D O I
10.1073/pnas.1912858116
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.
引用
收藏
页码:21715 / 21726
页数:12
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