The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space

Nature Medicine
Johanna KlughammerChristoph Bock

Abstract

Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data co...Continue Reading

References

Oct 26, 2005·Neoplasia : an International Journal for Oncology Research·Silke WemmertSteffi Urbschat
Dec 31, 2005·Nucleic Acids Research·A S HinrichsW J Kent
Jul 5, 2008·Nature·Alexander MeissnerEric S Lander
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jun 30, 2009·Journal of Neuro-oncology·Adelheid WöhrerJohannes Andreas Hainfellner
Jul 29, 2009·BMC Bioinformatics·Yuanxin Xi, Wei Li
Dec 10, 2009·Nature Reviews. Neurology·Michael WellerMonika E Hegi
Jan 19, 2010·Bioinformatics·Heng Li, Richard Durbin
Mar 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick Y WenSusan M Chang
Sep 21, 2010·Nature Biotechnology·Christoph BockAlexander Meissner
Dec 6, 2011·Cancer Cell·Matija SnuderlA John Iafrate
Jun 9, 2012·Stem Cells and Development·Christoph P BeierDagmar Beier
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Sep 8, 2012·Genome Research·Jennifer HarrowTim J Hubbard
Sep 19, 2012·Nature Reviews. Genetics·Christoph Bock
Feb 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andrea SottorivaSimon Tavaré
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Apr 17, 2013·BMC Bioinformatics·Edward Y ChenAvi Ma'ayan
Jun 7, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael ProsniakD Craig Hooper
Jul 9, 2013·Diagnostic Pathology·Christophe DeroulersMarc Lartaud
Oct 15, 2013·Cell·Cameron W BrennanUNKNOWN TCGA Research Network
Feb 21, 2014·The New England Journal of Medicine·Mark R GilbertMinesh P Mehta
Feb 21, 2014·The New England Journal of Medicine·Olivier L ChinotTimothy Cloughesy
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
May 9, 2014·PloS One·Nicole PorzRoland Wiest
Jun 14, 2014·Science·Anoop P PatelBradley E Bernstein
Jul 30, 2014·Cell Reports·David BrocksUNKNOWN ICGC Early Onset Prostate Cancer Project
Sep 28, 2014·Genome Biology·Sheng LiChristopher E Mason
Sep 30, 2014·Nature Methods·Yassen AssenovChristoph Bock
Jan 7, 2015·Proceedings of the National Academy of Sciences of the United States of America·Mona MeyerPeter B Dirks
Feb 20, 2015·Nature·UNKNOWN Roadmap Epigenomics ConsortiumManolis Kellis
Apr 19, 2015·Genome Biology·Thomas KuilmanOscar Krijgsman
Jul 15, 2015·Molecular Reproduction and Development·Johannes SchindelinKevin W Eliceiri
Jul 21, 2015·Nature Medicine·Andrew J GentlesAsh A Alizadeh

❮ Previous
Next ❯

Citations

Jan 5, 2019·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Kenta MasuiNoriyuki Shibata
Feb 27, 2019·Archives of Pharmacal Research·Jong Woo Park, Jeung-Whan Han
Feb 24, 2019·Bioinformatics·Pietro Di LenaChristine Nardini
Aug 4, 2019·Pathology Oncology Research : POR·Zoltan Kraboth, Bernadette Kalman
Sep 11, 2019·American Journal of Epidemiology·Harriet L MillsKate Tilling
Nov 20, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kaspar DraaismaPim J French
Jan 20, 2020·Neuropathology and Applied Neurobiology·E Perez, D Capper
Feb 28, 2020·Nucleic Acids Research·Michael SchererMarkus List
Mar 3, 2020·Expert Review of Anticancer Therapy·Asgeir Store JakolaOle Solheim
Mar 12, 2020·Human Molecular Genetics·Silke SzymczakAlmut Nebel
May 27, 2020·Journal of Neuro-oncology·Debanjan BhattacharyaSoma Sengupta
Aug 13, 2020·CNS Neuroscience & Therapeutics·Aleksandra Majchrzak-CelińskaAnna-Maria Barciszewska
Apr 17, 2020·Neuro-oncology·Teresa G KriegerChristian Conrad
Mar 16, 2019·Genome Biology·Fabian MüllerChristoph Bock
Mar 2, 2019·NPJ Precision Oncology·Francisco Azuaje
Oct 18, 2019·Wiener klinische Wochenschrift
Jun 21, 2020·Cancers·Thomas RoetzerAdelheid Woehrer
Jun 5, 2019·Genes & Development·Ryan C GimpleJeremy N Rich
Apr 11, 2019·Epigenetics Insights·Javier Ij OrozcoDiego M Marzese
Jan 16, 2020·Genome Medicine·Eoghan R MaloneLillian L Siu
Jun 14, 2020·Signal Transduction and Targeted Therapy·Ling ChenYongguang Tao
Jul 15, 2020·Nature Genetics·Shuang G ZhaoFelix Y Feng
Aug 12, 2020·Journal of Cancer Research and Clinical Oncology·Zoltan KrabothBernadette Kalman
May 13, 2020·Cancer Metastasis Reviews·Alejandra I FerrerPranela Rameshwar
Oct 24, 2018·International Journal of Molecular Sciences·Mio HarachiNoriyuki Shibata
Apr 5, 2020·Cancers·Zhen Dong, Hongjuan Cui
Feb 27, 2020·Hepatology International·H TaghizadehG W Prager
Sep 10, 2020·Frontiers in Pharmacology·Sandip Kumar PatelVineeta Rai
Nov 22, 2019·The EMBO Journal·Solomiia KorchynskaTibor Harkany
Jul 26, 2019·Annals of Surgical Oncology·Maggie L DiNomeDiego M Marzese
Nov 7, 2019·Biomarker Research·Mingzhou GuoJames G Herman
Jul 31, 2020·International Journal of Molecular Sciences·Barbora VitovcovaEmil Rudolf
Dec 29, 2019·Scientific Reports·H TaghizadehG W Prager
Sep 19, 2020·Journal of Experimental & Clinical Cancer Research : CR·Yuhao ZhangHong Wang
Aug 9, 2020·Frontiers in Immunology·Syreeta DeCordovaUday Kishore

❮ Previous
Next ❯

Datasets Mentioned

BETA
EK078-2004
GSE100351
EGAS00001002538

Methods Mentioned

BETA
methylation sequencing
methylation profiling
RRBS
methylation
RNA-seq
single-cell sequencing
methylation assay
PCR
chips
electrophoresis

Software Mentioned

LiblineaR
Enrichr
MATLAB
CNVkit
Fiji
R package ‘ ggplot2 ’
Pypiper
RnBeads
liftOver
R script

Related Concepts

Related Feeds

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.