Spatiotemporal genomic architecture informs precision oncology in glioblastoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04

AUTHORS

Jin-Ku Lee, Jiguang Wang, Jason K Sa, Erik Ladewig, Hae-Ock Lee, In-Hee Lee, Hyun Ju Kang, Daniel S Rosenbloom, Pablo G Camara, Zhaoqi Liu, Patrick van Nieuwenhuizen, Sang Won Jung, Seung Won Choi, Junhyung Kim, Andrew Chen, Kyu-Tae Kim, Sang Shin, Yun Jee Seo, Jin-Mi Oh, Yong Jae Shin, Chul-Kee Park, Doo-Sik Kong, Ho Jun Seol, Andrew Blumberg, Jung-Il Lee, Antonio Iavarone, Woong-Yang Park, Raul Rabadan, Do-Hyun Nam

ABSTRACT

Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies. However, this proposition is complicated by spatial and temporal heterogeneity. 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. More... »

PAGES

594-599

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3806

    DOI

    http://dx.doi.org/10.1038/ng.3806

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084129146

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28263318


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