CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Brain Neoplasms
/ genetics
Chromosomes, Human, Pair 1
/ genetics
Chromosomes, Human, Pair 19
/ genetics
Cohort Studies
Combined Modality Therapy
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Female
Follow-Up Studies
Glioma
/ genetics
Homozygote
Humans
Isocitrate Dehydrogenase
/ genetics
Male
Middle Aged
Mutation
Prognosis
Sequence Deletion
Survival Rate
Young Adult
CDKN2A homozygous deletion
IDH-mutant
IDH-mutant and 1p/19q codeleted
anaplastic astrocytoma
anaplastic oligodendroglioma
glioblastoma
microvascular proliferation
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
17 12 2019
17 12 2019
Historique:
pubmed:
14
12
2019
medline:
19
8
2020
entrez:
14
12
2019
Statut:
ppublish
Résumé
The 2016 World Health Organization (WHO) classification of central nervous system tumors stratifies isocitrate dehydrogenase (IDH)-mutant gliomas into 2 major groups depending on the presence or absence of 1p/19q codeletion. However, the grading system remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification. In a large cohort of 911 high-grade IDH-mutant gliomas from the French national POLA network (including 428 IDH-mutant gliomas without 1p/19q codeletion and 483 anaplastic oligodendrogliomas, IDH-mutant and 1p/19q codeleted), we investigated the prognostic value of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene homozygous deletion as well as WHO grading criteria (mitoses, microvascular proliferation, and necrosis). In addition, we searched for other retinoblastoma pathway gene alterations (CDK4 amplification and RB1 homozygous deletion) in a subset of patients. CDKN2A homozygous deletion was also searched in an independent series of 40 grade II IDH-mutant gliomas. CDKN2A homozygous deletion was associated with dismal outcome among IDH-mutant gliomas lacking 1p/19q codeletion (P < 0.0001 for progression-free survival and P = 0.004 for overall survival) as well as among anaplastic oligodendrogliomas, IDH-mutant + 1p/19q codeleted (P = 0.002 for progression-free survival and P < 0.0001 for overall survival) in univariate and multivariate analysis including age, extent of surgery, adjuvant treatment, microvascular proliferation, and necrosis. In both groups, the presence of microvascular proliferation and/or necrosis remained of prognostic value only in cases lacking CDKN2A homozygous deletion. CDKN2A homozygous deletion was not recorded in grade II gliomas. Our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the 2 broad categories of IDH-mutant gliomas stratified on 1p/19q codeletion and suggests that the grading of these tumors should be refined.
Sections du résumé
BACKGROUND
The 2016 World Health Organization (WHO) classification of central nervous system tumors stratifies isocitrate dehydrogenase (IDH)-mutant gliomas into 2 major groups depending on the presence or absence of 1p/19q codeletion. However, the grading system remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification.
METHODS
In a large cohort of 911 high-grade IDH-mutant gliomas from the French national POLA network (including 428 IDH-mutant gliomas without 1p/19q codeletion and 483 anaplastic oligodendrogliomas, IDH-mutant and 1p/19q codeleted), we investigated the prognostic value of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene homozygous deletion as well as WHO grading criteria (mitoses, microvascular proliferation, and necrosis). In addition, we searched for other retinoblastoma pathway gene alterations (CDK4 amplification and RB1 homozygous deletion) in a subset of patients. CDKN2A homozygous deletion was also searched in an independent series of 40 grade II IDH-mutant gliomas.
RESULTS
CDKN2A homozygous deletion was associated with dismal outcome among IDH-mutant gliomas lacking 1p/19q codeletion (P < 0.0001 for progression-free survival and P = 0.004 for overall survival) as well as among anaplastic oligodendrogliomas, IDH-mutant + 1p/19q codeleted (P = 0.002 for progression-free survival and P < 0.0001 for overall survival) in univariate and multivariate analysis including age, extent of surgery, adjuvant treatment, microvascular proliferation, and necrosis. In both groups, the presence of microvascular proliferation and/or necrosis remained of prognostic value only in cases lacking CDKN2A homozygous deletion. CDKN2A homozygous deletion was not recorded in grade II gliomas.
CONCLUSIONS
Our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the 2 broad categories of IDH-mutant gliomas stratified on 1p/19q codeletion and suggests that the grading of these tumors should be refined.
Identifiants
pubmed: 31832685
pii: 5531923
doi: 10.1093/neuonc/noz124
pmc: PMC7145561
doi:
Substances chimiques
Biomarkers, Tumor
0
CDKN2A protein, human
0
Cyclin-Dependent Kinase Inhibitor p16
0
IDH2 protein, human
EC 1.1.1.41
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1519-1528Investigateurs
C Desenclos
(C)
H Sevestre
(H)
P Menei
(P)
A Rousseau
(A)
T Cruel
(T)
S Lopez
(S)
M-I Mihai
(MI)
A Petit
(A)
C Adam
(C)
F Parker
(F)
P Dam-Hieu
(P)
I Quintin-Roué
(I)
S Eimer
(S)
H Loiseau
(H)
L Bekaert
(L)
F Chapon
(F)
D Ricard
(D)
C Godfraind
(C)
T Khallil
(T)
D Cazals-Hatem
(D)
T Faillot
(T)
C Gaultier
(C)
M C Tortel
(MC)
I Carpiuc
(I)
P Richard
(P)
W Lahiani
(W)
H Aubriot-Lorton
(H)
F Ghiringhelli
(F)
C A Maurage
(CA)
C Ramirez
(C)
E M Gueye
(EM)
F Labrousse
(F)
O Chinot
(O)
L Bauchet
(L)
V Rigau
(V)
P Beauchesne
(P)
G Gauchotte
(G)
M Campone
(M)
D Loussouarn
(D)
D Fontaine
(D)
F Vandenbos-Burel
(F)
A Le Floch
(A)
P Roger
(P)
C Blechet
(C)
M Fesneau
(M)
A Carpentier
(A)
J Y Delattre
(JY)
S Elouadhani-Hamdi
(S)
M Polivka
(M)
D Larrieu-Ciron
(D)
S Milin
(S)
P Colin
(P)
M D Diebold
(MD)
D Chiforeanu
(D)
E Vauleon
(E)
O Langlois
(O)
A Laquerriere
(A)
F Forest
(F)
M J Motso-Fotso
(MJ)
M Andraud
(M)
G Runavot
(G)
B Lhermitte
(B)
G Noel
(G)
S Gaillard
(S)
C Villa
(C)
N Desse
(N)
C Rousselot-Denis
(C)
I Zemmoura
(I)
E Cohen-Moyal
(E)
E Uro-Coste
(E)
F Dhermain
(F)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
Nature. 1993 Dec 16;366(6456):704-7
pubmed: 8259215
Acta Neuropathol. 2016 Oct;132(4):625-34
pubmed: 27573687
EMBO J. 1998 Sep 1;17(17):5001-14
pubmed: 9724636
Neurology. 2015 Oct 13;85(15):1325-31
pubmed: 26385879
Acta Neuropathol Commun. 2015 Jun 20;3:34
pubmed: 26091668
Neuro Oncol. 2019 Jun 10;21(6):819-821
pubmed: 30918961
Neuropathology. 2013 Aug;33(4):405-12
pubmed: 23311918
Cancer Cell. 2016 May 9;29(5):737-750
pubmed: 27165745
Neuropathol Appl Neurobiol. 2019 Feb;45(2):108-118
pubmed: 30326163
Nat Genet. 2015 May;47(5):458-68
pubmed: 25848751
J Neuropathol Exp Neurol. 2015 May;74(5):442-52
pubmed: 25853694
J Clin Oncol. 2013 Jan 20;31(3):344-50
pubmed: 23071237
Biostatistics. 2014 Oct;15(4):757-73
pubmed: 24728979
Acta Neuropathol. 2018 Jul;136(1):153-166
pubmed: 29687258
Neuro Oncol. 2018 Jan 10;20(1):66-77
pubmed: 29016839
J Clin Oncol. 2014 Mar 10;32(8):783-90
pubmed: 24516018
Acta Neuropathol. 2015 Jun;129(6):867-73
pubmed: 25962792
Acta Neuropathol. 2017 Jun;133(6):1001-1016
pubmed: 28255664
Acta Neuropathol Commun. 2017 May 22;5(1):39
pubmed: 28532485
Oncotarget. 2016 Apr 19;7(16):21190-8
pubmed: 27049832
Acta Neuropathol. 2015 Apr;129(4):585-96
pubmed: 25701198
Neurology. 2007 May 22;68(21):1831-6
pubmed: 17515545
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
N Engl J Med. 2015 Jun 25;372(26):2481-98
pubmed: 26061751
Science. 1996 Dec 6;274(5293):1672-7
pubmed: 8939849