We studied how intratumoral genetic heterogeneity shapes tumor growth and therapy response for isocitrate dehydrogenase (IDH)-wild-type glioblastoma, a rapidly regrowing tumor. We inferred the evolutionary trajectories of matched pairs of primary and relapsed tumors based on deep whole-genome-sequencing data. This analysis suggests both a distant origin of de novo glioblastoma, up to 7 years before diagnosis, and a common path of early tumorigenesis, with one or more of chromosome 7 gain, 9p loss, or 10 loss, at tumor initiation. TERT promoter mutations often occurred later as a prerequisite for rapid growth. In contrast to this common early path, relapsed tumors acquired no stereotypical pattern of mutations and typically regrew from oligoclonal origins, suggesting sparse selective pressure by therapeutic measures.
Description
Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis. - PubMed - NCBI
%0 Journal Article
%1 Korber:2019:Cancer-Cell:30905762
%A Körber, V
%A Yang, J
%A Barah, P
%A Wu, Y
%A Stichel, D
%A Gu, Z
%A Fletcher, M N C
%A Jones, D
%A Hentschel, B
%A Lamszus, K
%A Tonn, J C
%A Schackert, G
%A Sabel, M
%A Felsberg, J
%A Zacher, A
%A Kaulich, K
%A Hübschmann, D
%A Herold-Mende, C
%A von Deimling, A
%A Weller, M
%A Radlwimmer, B
%A Schlesner, M
%A Reifenberger, G
%A Höfer, T
%A Lichter, P
%D 2019
%J Cancer Cell
%K cancer-research development glioblastoma
%N 4
%P 692-704
%R 10.1016/j.ccell.2019.02.007
%T Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis
%U https://www.ncbi.nlm.nih.gov/pubmed/30905762
%V 35
%X We studied how intratumoral genetic heterogeneity shapes tumor growth and therapy response for isocitrate dehydrogenase (IDH)-wild-type glioblastoma, a rapidly regrowing tumor. We inferred the evolutionary trajectories of matched pairs of primary and relapsed tumors based on deep whole-genome-sequencing data. This analysis suggests both a distant origin of de novo glioblastoma, up to 7 years before diagnosis, and a common path of early tumorigenesis, with one or more of chromosome 7 gain, 9p loss, or 10 loss, at tumor initiation. TERT promoter mutations often occurred later as a prerequisite for rapid growth. In contrast to this common early path, relapsed tumors acquired no stereotypical pattern of mutations and typically regrew from oligoclonal origins, suggesting sparse selective pressure by therapeutic measures.
@article{Korber:2019:Cancer-Cell:30905762,
abstract = {We studied how intratumoral genetic heterogeneity shapes tumor growth and therapy response for isocitrate dehydrogenase (IDH)-wild-type glioblastoma, a rapidly regrowing tumor. We inferred the evolutionary trajectories of matched pairs of primary and relapsed tumors based on deep whole-genome-sequencing data. This analysis suggests both a distant origin of de novo glioblastoma, up to 7 years before diagnosis, and a common path of early tumorigenesis, with one or more of chromosome 7 gain, 9p loss, or 10 loss, at tumor initiation. TERT promoter mutations often occurred later as a prerequisite for rapid growth. In contrast to this common early path, relapsed tumors acquired no stereotypical pattern of mutations and typically regrew from oligoclonal origins, suggesting sparse selective pressure by therapeutic measures.},
added-at = {2019-06-08T21:10:58.000+0200},
author = {K{\"o}rber, V and Yang, J and Barah, P and Wu, Y and Stichel, D and Gu, Z and Fletcher, M N C and Jones, D and Hentschel, B and Lamszus, K and Tonn, J C and Schackert, G and Sabel, M and Felsberg, J and Zacher, A and Kaulich, K and H{\"u}bschmann, D and Herold-Mende, C and von Deimling, A and Weller, M and Radlwimmer, B and Schlesner, M and Reifenberger, G and H{\"o}fer, T and Lichter, P},
biburl = {https://www.bibsonomy.org/bibtex/27d0a8c88d1c973e8043bae8216774d2d/marcsaric},
description = {Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis. - PubMed - NCBI},
doi = {10.1016/j.ccell.2019.02.007},
interhash = {d2ff21575520521c4af1c863f0f6fe92},
intrahash = {7d0a8c88d1c973e8043bae8216774d2d},
journal = {Cancer Cell},
keywords = {cancer-research development glioblastoma},
month = apr,
number = 4,
pages = {692-704},
pmid = {30905762},
timestamp = {2019-06-08T21:10:58.000+0200},
title = {Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30905762},
volume = 35,
year = 2019
}