期刊
NATURE GENETICS
卷 49, 期 5, 页码 780-+出版社
NATURE PORTFOLIO
DOI: 10.1038/ng.3838
关键词
-
资金
- Genome Canada
- Genome BC
- Terry Fox Research Institute
- Ontario Institute for Cancer Research
- Pediatric Oncology Group Ontario
- funds from The Family of Kathleen Lorette
- Clark H. Smith Brain Tumour Centre
- Montreal Children's Hospital Foundation
- Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre
- Cancer Genetics Program
- Garron Family Cancer Centre
- B.R.A.I.N. Child
- M.D.T.'s Garron Family Endowment
- BC Childhood Cancer Parents Association
- Stand Up To Cancer St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113]
- Garron Family Chair in Childhood Cancer Research
- Cure Search Foundation
- US National Institutes of Health [R01CA148699, R01CA159859]
- Pediatric Brain Tumor Foundation
- Brainchild
- Ontario Institute for Cancer Research - Government of Ontario
- Brain Tumour Foundation of Canada Impact Grant of the Canadian Cancer Society
- Brain Canada
- Health Canada [703202]
- CureSearch for Children's Cancer
- PedBrain Tumor Project - German Cancer Aid [109252]
- German Federal Ministry of Education and Research (BMBF) [01KU1201A, MedSys 0315416C]
- B.R.A.I.N. Child and Megan's Walk
- Canadian Institutes of Health Research (CIHR) [FDN-143288]
- Dr. Mildred Scheel Foundation for Cancer Research/German Cancer Aid
- Stephen Buttrum Brain Tumour Research Fellowship - Brain Tumour Foundation of Canada
- CIHR
- Alberta Innovates-Health Solutions
- The Francis Crick Institute [10002] Funding Source: researchfish
Spatial heterogeneity of transcriptional and genetic markers between physically isolated biopsies of a single tumor poses major barriers to the identification of biomarkers and the development of targeted therapies that will be effective against the entire tumor. We analyzed the spatial heterogeneity of multiregional biopsies from 35 patients, using a combination of transcriptomic and genomic profiles. Medulloblastomas (MBs), but not high-grade gliomas (HGGs), demonstrated spatially homogeneous transcriptomes, which allowed for accurate subgrouping of tumors from a single biopsy. Conversely, somatic mutations that affect genes suitable for targeted therapeutics demonstrated high levels of spatial heterogeneity in MB, malignant glioma, and renal cell carcinoma (RCC). Actionable targets found in a single MB biopsy were seldom clonal across the entire tumor, which brings the efficacy of monotherapies against a single target into question. Clinical trials of targeted therapies for MB should first ensure the spatially ubiquitous nature of the target mutation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据