Spatiotemporal genomic architecture informs precision oncology in glioblastomaopen access
- Authors
- Lee, Jin-Ku; Wang, Jiguang; Sa, Jason K.; Ladewig, Erik; Lee, Hae-Ock; Lee, In-Hee; Kang, Hyun Ju; Rosenbloom, Daniel S.; Camara, Pablo G.; Liu, Zhaoqi; van Nieuwenhuizen, Patrick; Jung, Sang Won; Choi, Seung Won; Kim, Junhyung; Chen, Andrew; Kim, Kyu-Tae; Shin, Sang; Seo, Yun Jee; Oh, Jin-Mi; Shin, Yong Jae; Park, Chul-Kee; Kong, Doo-Sik; Seol, Ho Jun; Blumberg, Andrew; Lee, Jung-Il; Iavarone, Antonio; Park, Woong-Yang; Rabadan, Raul; Nam, Do-Hyun
- Issue Date
- Apr-2017
- Publisher
- Nature Publishing Group
- Citation
- Nature Genetics, v.49, no.4, pp 594 - 599
- Pages
- 6
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Nature Genetics
- Volume
- 49
- Number
- 4
- Start Page
- 594
- End Page
- 599
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/5119
- DOI
- 10.1038/ng.3806
- ISSN
- 1061-4036
1546-1718
- Abstract
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 3. Graduate School > Biomedical Research Center > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.