Spatiotemporal genomic architecture informs precision oncology in glioblastoma

被引：234

作者：

Lee, Jin-Ku ^{[1
,2
]}

Wang, Jiguang ^{[3
,4
,5
]}

Sa, Jason K. ^{[1
,2
,6
]}

Ladewig, Erik ^{[3
,4
]}

Lee, Hae-Ock ^{[7
]}

Lee, In-Hee ^{[1
,2
]}

Kang, Hyun Ju ^{[1
,2
]}

Rosenbloom, Daniel S. ^{[3
,4
]}

Camara, Pablo G. ^{[3
,4
]}

Liu, Zhaoqi ^{[3
,4
]}

van Nieuwenhuizen, Patrick ^{[3
,4
]}

Jung, Sang Won ^{[1
,2
,6
]}

Choi, Seung Won ^{[1
,2
,6
]}

Kim, Junhyung ^{[1
,2
]}

Chen, Andrew ^{[3
,4
]}

Kim, Kyu-Tae ^{[7
]}

Shin, Sang ^{[1
,2
,6
]}

Seo, Yun Jee ^{[1
,2
]}

Oh, Jin-Mi ^{[1
,2
]}

Shin, Yong Jae ^{[1
,2
,7
]}

Park, Chul-Kee ^{[8
,9
]}

Kong, Doo-Sik ^{[2
]}

Seol, Ho Jun ^{[2
]}

Blumberg, Andrew ^{[10
]}

Lee, Jung-Il ^{[2
]}

Iavarone, Antonio ^{[11
,12
,13
]}

Park, Woong-Yang ^{[6
,7
]}

Rabadan, Raul ^{[3
,4
]}

Nam, Do-Hyun ^{[1
,2
]}

机构：

[1] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Inst Refractory Canc Res, Seoul, South Korea

[2] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Neurosurg, Seoul, South Korea

[3] Columbia Univ, Dept Syst Biol, New York, NY USA

[4] Columbia Univ, Dept Biomed Informat, New York, NY USA

[5] Hong Kong Univ Sci & Technol, Div Life Sci & Biomed Engn, Hong Kong, Peoples R China

[6] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul, South Korea

[7] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Samsung Genome Inst, Seoul, South Korea

[8] Seoul Natl Univ, Coll Med, Dept Neurosurg, Seoul, South Korea

[9] Seoul Natl Univ Hosp, Seoul, South Korea

[10] Univ Texas, Dept Math, Austin, TX USA

[11] Columbia Univ, Inst Canc Genet, New York, NY USA

[12] Columbia Univ, Dept Neurol, New York, NY USA

[13] Columbia Univ, Dept Pathol, New York, NY 10027 USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 04期

关键词：

FLUORESCENCE-GUIDED SURGERY; INTRATUMORAL HETEROGENEITY; 5-AMINOLEVULINIC ACID; REVEALS; GENES; LANDSCAPE; EVOLUTION; GLIOMA; QUANTIFICATION; IDENTIFICATION;

D O I：

10.1038/ng.3806

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies1-5. However, this proposition is complicated by spatial and temporal heterogeneity6-14. Here we study genomic and expression profiles across 127 multisector or longitudinal specimens from 52 individuals with glioblastoma (GBM). Using bulk and single-cell data, we find that samples from the same tumor mass share genomic and expression signatures, whereas geographically separated, multifocal tumors and/or long-term recurrent tumors are seeded from different clones. Chemical screening of patient-derived glioma cells (PDCs) shows that therapeutic response is associated with genetic similarity, and multifocal tumors that are enriched with PIK3CA mutations have a heterogeneous drug-response pattern. We show that targeting truncal events is more efficacious than targeting private events in reducing the tumor burden. In summary, this work demonstrates that evolutionary inference from integrated genomic analysis in multisector biopsies can inform targeted therapeutic interventions for patients with GBM.

引用

页码：594 / +

页数：9

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