The genomic landscape of tuberous sclerosis complex

被引：169

作者：

Martin, Katie R. ^{[1
]}

Zhou, Wanding ^{[2
]}

Bowman, Megan J. ^{[3
]}

Shih, Juliann ^{[4
]}

Au, Kit Sing ^{[5
]}

Dittenhafer-Reed, Kristin E. ^{[1
]}

Sisson, Kellie A. ^{[1
]}

Koeman, Julie ^{[6
]}

Weisenberger, Daniel J. ^{[7
]}

Cottingham, Sandra L. ^{[8
]}

DeRoos, Steven T. ^{[9
]}

Devinsky, Orrin ^{[10
]}

Winn, Mary E. ^{[3
]}

Cherniack, Andrew D. ^{[4
]}

Shen, Hui ^{[2
]}

Northrup, Hope ^{[5
]}

Krueger, Darcy A. ^{[11
]}

MacKeigan, Jeffrey P. ^{[1
,12
]}

机构：

[1] Van Andel Res Inst, Ctr Canc & Cell Biol, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA

[2] Van Andel Res Inst, Ctr Epigenet, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA

[3] Van Andel Res Inst, Bioinformat & Biostat Core, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA

[4] Broad Inst Harvard & MIT, Canc Program, 415 Main St, Cambridge, MA 02142 USA

[5] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, McGovern Med Sch, 6431 Fannin, Houston, TX 77030 USA

[6] Van Andel Res Inst, Cytogenet & Pathol Core, 333 Bostwick Ave NE, Grand Rapids, MI 49503 USA

[7] Univ Southern Calif, Norris Comprehens Canc Ctr, 1450 Biggy St, Los Angeles, CA 90033 USA

[8] Spectrum Hlth Syst, Dept Pathol, 100 Michigan St NE, Grand Rapids, MI 49503 USA

[9] Spectrum Hlth Syst, Helen DeVos Childrens Hosp, Div Pediat Neurol, 100 Michigan St NE, Grand Rapids, MI 49503 USA

[10] NYU, Dept Neurol, Sch Med, 223 E 34 St, New York, NY 10016 USA

[11] Cincinnati Childrens Hosp Med Ctr, Div Neurol, 3333 Burnet Ave, Cincinnati, OH 45229 USA

[12] Michigan State Univ, Coll Human Med, 220 Trowbridge Rd, E Lansing, MI 48824 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

GIANT-CELL ASTROCYTOMAS; MUTATIONAL ANALYSIS; GENE-EXPRESSION; CORTICAL TUBERS; TSC1; IDENTIFICATION; LESIONS; ANGIOMYOLIPOMA; EVEROLIMUS; DEFICITS;

D O I：

10.1038/ncomms15816

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：

Tuberous sclerosis complex (TSC) is a rare genetic disease causing multisystem growth of benign tumours and other hamartomatous lesions, which leads to diverse and debilitating clinical symptoms. Patients are born with TSC1 or TSC2 mutations, and somatic inactivation of wild-type alleles drives MTOR activation; however, second hits to TSC1/TSC2 are not always observed. Here, we present the genomic landscape of TSC hamartomas. We determine that TSC lesions contain a low somatic mutational burden relative to carcinomas, a subset feature large-scale chromosomal aberrations, and highly conserved molecular signatures for each type exist. Analysis of the molecular signatures coupled with computational approaches reveals unique aspects of cellular heterogeneity and cell origin. Using immune data sets, we identify significant neuroinflammation in TSC-associated brain tumours. Taken together, this molecular catalogue of TSC serves as a resource into the origin of these hamartomas and provides a framework that unifies genomic and transcriptomic dimensions for complex tumours.

引用

页数：13

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