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Longitudinal molecular trajectories of diffuse glioma in adults

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers acros... Full description

Journal Title: Nature Dec 5, 2019, Vol.576(7785), pp.112-3,120A-120P
Main Author: Barthel, Floris
Other Authors: Johnson, Kevin , Varn, Frederick , Moskalik, Anzhela , Tanner, Georgette , Kocakavuk, Emre , Anderson, Kevin , Abiola, Olajide , Aldape, Kenneth , Alfaro, Kristin , Alpar, Donat , Amin, Samirkumar , Ashley, David , Bandopadhayay, Pratiti , Barnholtz-Sloan, Jill , Beroukhim, Rameen , Bock, Christoph , Brastianos, Priscilla , Brat, Daniel , Brodbelt
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 00280836 ; E-ISSN: 14764687 ; DOI: 10.1038/s41586-019-1775-1
Link: http://search.proquest.com/docview/2326824640/?pq-origsite=primo
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title: Longitudinal molecular trajectories of diffuse glioma in adults
format: Article
creator:
  • Barthel, Floris
  • Johnson, Kevin
  • Varn, Frederick
  • Moskalik, Anzhela
  • Tanner, Georgette
  • Kocakavuk, Emre
  • Anderson, Kevin
  • Abiola, Olajide
  • Aldape, Kenneth
  • Alfaro, Kristin
  • Alpar, Donat
  • Amin, Samirkumar
  • Ashley, David
  • Bandopadhayay, Pratiti
  • Barnholtz-Sloan, Jill
  • Beroukhim, Rameen
  • Bock, Christoph
  • Brastianos, Priscilla
  • Brat, Daniel
  • Brodbelt
subjects:
  • DNA Methylation
  • DNA Sequencing
  • Vaccines
  • Chromosomes
  • Stochasticity
  • Datasets
  • Brain Cancer
  • Alkylation
  • Bioinformatics
  • Gene Deletion
  • Chromosome Deletion
  • Cancer Therapies
  • Mutation
  • Clonal Deletion
  • Phenotypes
  • Survival
  • Mutation
  • Aneuploidy
  • Tumors
  • Mutation
ispartof: Nature, Dec 5, 2019, Vol.576(7785), pp.112-3,120A-120P
description: The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar...
language: eng
source:
identifier: ISSN: 00280836 ; E-ISSN: 14764687 ; DOI: 10.1038/s41586-019-1775-1
fulltext: fulltext
issn:
  • 00280836
  • 0028-0836
  • 14764687
  • 1476-4687
url: Link


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titleLongitudinal molecular trajectories of diffuse glioma in adults
creatorBarthel, Floris ; Johnson, Kevin ; Varn, Frederick ; Moskalik, Anzhela ; Tanner, Georgette ; Kocakavuk, Emre ; Anderson, Kevin ; Abiola, Olajide ; Aldape, Kenneth ; Alfaro, Kristin ; Alpar, Donat ; Amin, Samirkumar ; Ashley, David ; Bandopadhayay, Pratiti ; Barnholtz-Sloan, Jill ; Beroukhim, Rameen ; Bock, Christoph ; Brastianos, Priscilla ; Brat, Daniel ; Brodbelt
ispartofNature, Dec 5, 2019, Vol.576(7785), pp.112-3,120A-120P
identifier
subjectDNA Methylation ; DNA Sequencing ; Vaccines ; Chromosomes ; Stochasticity ; Datasets ; Brain Cancer ; Alkylation ; Bioinformatics ; Gene Deletion ; Chromosome Deletion ; Cancer Therapies ; Mutation ; Clonal Deletion ; Phenotypes ; Survival ; Mutation ; Aneuploidy ; Tumors ; Mutation
descriptionThe evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar...
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titleLongitudinal molecular trajectories of diffuse glioma in adults
descriptionThe evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar...
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citationpf 112 pt 3 vol 576 issue 7785
lsr30VSR-Enriched:[pqid, pages]
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titleLongitudinal molecular trajectories of diffuse glioma in adults
authorBarthel, Floris ; Johnson, Kevin ; Varn, Frederick ; Moskalik, Anzhela ; Tanner, Georgette ; Kocakavuk, Emre ; Anderson, Kevin ; Abiola, Olajide ; Aldape, Kenneth ; Alfaro, Kristin ; Alpar, Donat ; Amin, Samirkumar ; Ashley, David ; Bandopadhayay, Pratiti ; Barnholtz-Sloan, Jill ; Beroukhim, Rameen ; Bock, Christoph ; Brastianos, Priscilla ; Brat, Daniel ; Brodbelt
creationdate20191205
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0DNA Methylation
1DNA Sequencing
2Vaccines
3Chromosomes
4Stochasticity
5Datasets
6Brain Cancer
7Alkylation
8Bioinformatics
9Gene Deletion
10Chromosome Deletion
11Cancer Therapies
12Mutation
13Clonal Deletion
14Phenotypes
15Survival
16Aneuploidy
17Tumors
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7Science Database (Alumni edition)
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9Health & Medical Collection
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14Ecology Abstracts
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16Animal Behavior Abstracts
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22Engineering Database
23Biological Science Database
24Environmental Science Database (ProQuest)
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83Zadeh, Gelareh
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12Ashley, David
13Bandopadhayay, Pratiti
14Barnholtz-Sloan, Jill
15Beroukhim, Rameen
16Bock, Christoph
17Brastianos, Priscilla
18Brat, Daniel
19Brodbelt, Andrew
20Bruns, Alexander
21Bulsara, Ketan
22Chakrabarty, Aruna
23Chakravarti, Arnab
24Chuang, Jeffrey
25Claus, Elizabeth
26Cochran, Elizabeth
27Connelly, Jennifer
28Costello, Joseph
29Finocchiaro, Gaetano
30Fletcher, Michael
31French, Pim
32Gan, Hui
33Gilbert, Mark
34Gould, Peter
35Grimmer, Matthew
36Iavarone, Antonio
37Ismail, Azzam
38Jenkinson, Michael
39Khasraw, Mustafa
40Kim, Hoon
41M Kouwenhoven, Mathilde
42Laviolette, Peter
43Li, Meihong
44Lichter, Peter
45Ligon, Keith
46Lowman, Allison
47Malta, Tathiane
48Mazor, Tali
49Mcdonald, Kerrie
50Molinaro, Annette
51Nam, Do-Hyun
52Nayyar, Naema
53Ng, Ho
54Ngan, Chew
55Niclou, Simone
56Niers, Johanna
57Noushmehr, Houtan
58Noorbakhsh, Javad
59Ormond, D
60Park, Chul-Kee
61Poisson, Laila
62Rabadan, Raul
63Radlwimmer, Bernhard
64Rao, Ganesh
65Reifenberger, Guido
66Sa, Jason
67Schuster, Michael
68Shaw, Brian
69Short, Susan
70Smitt, Peter
71Sloan, Andrew
72Smits, Marion
73Suzuki, Hiromichi
74Tabatabai, Ghazaleh
75Vanmeir, Erwin
76Watts, Colin
77Weller, Michael
78Wesseling, Pieter
79Westerman, Bart
80Widhalm, Georg
81Woehrer, Adelheid
82Yung, W
83Zadeh, Gelareh
84Huse, Jason
85De Groot, John
86Stead, Lucy
87Verhaak, Roel
88Kouwenhoven, Mathilde
89Van Meir, Erwin
atitleLongitudinal molecular trajectories of diffuse glioma in adults
jtitleNature
risdate20191205
volume576
issue7785
spage112
epage3
pages112-120
issn00280836
eissn14764687
formatjournal
genrearticle
ristypeJOUR
abstractThe evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar...
copLondon
pubNature Publishing Group
doi10.1038/s41586-019-1775-1
urlhttp://search.proquest.com/docview/2326824640/
date2019-12-05