Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

Adam M. Fontebasso; Margret Shirinian; Dong Anh Khuong-Quang; Denise Bechet; Tenzin Gayden; Marcel Kool; Nicolas De Jay; Karine Jacob; Noha Gerges; Barbara Hutter; Huriye Seker-Cin; Hendrik Witt; Alexandre Montpetit; Sébastien Brunet; Pierre Lepage; Geneviève Bourret; Almos Klekner; László Bognár; Peter Hauser; Miklós Garami; Jean Pierre Farmer; Jose Luis Montes; Jeffrey Atkinson; Sally Lambert; Tony Kwan; Andrey Korshunov; Uri Tabori; V. Peter Collins; Steffen Albrecht; Damien Faury; Stefan M. Pfister; Werner Paulus; Martin Hasselblatt; David T.W. Jones; Nada Jabado

doi:10.18632/oncotarget.5571

Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

Adam M. Fontebasso, Margret Shirinian, Dong Anh Khuong-Quang, Denise Bechet, Tenzin Gayden, Marcel Kool, Nicolas De Jay, Karine Jacob, Noha Gerges, Barbara Hutter, Huriye Seker-Cin, Hendrik Witt, Alexandre Montpetit, Sébastien Brunet, Pierre Lepage, Geneviève Bourret, Almos Klekner, László Bognár, Peter Hauser, Miklós GaramiJean Pierre Farmer, Jose Luis Montes, Jeffrey Atkinson, Sally Lambert, Tony Kwan, Andrey Korshunov, Uri Tabori, V. Peter Collins, Steffen Albrecht, Damien Faury, Stefan M. Pfister, Werner Paulus, Martin Hasselblatt, David T.W. Jones, Nada Jabado

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting noncerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2), whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.

Original language	English
Pages (from-to)	31844-31856
Number of pages	13
Journal	Oncotarget
Volume	6
Issue number	31
DOIs	https://doi.org/10.18632/oncotarget.5571
Publication status	Published - 2015
Externally published	Yes

Keywords

Aneuploidy
BRAF
MDM2
Pilocytic astrocytoma
PLK2

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10.18632/oncotarget.5571

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Fontebasso, A. M., Shirinian, M., Khuong-Quang, D. A., Bechet, D., Gayden, T., Kool, M., De Jay, N., Jacob, K., Gerges, N., Hutter, B., Seker-Cin, H., Witt, H., Montpetit, A., Brunet, S., Lepage, P., Bourret, G., Klekner, A., Bognár, L., Hauser, P., ... Jabado, N. (2015). Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age. Oncotarget, 6(31), 31844-31856. https://doi.org/10.18632/oncotarget.5571

@article{808eeb24a5734e4789fc8bd4885557ba,

title = "Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age",

abstract = "Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting noncerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2), whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.",

keywords = "Aneuploidy, BRAF, MDM2, Pilocytic astrocytoma, PLK2",

author = "Fontebasso, {Adam M.} and Margret Shirinian and Khuong-Quang, {Dong Anh} and Denise Bechet and Tenzin Gayden and Marcel Kool and {De Jay}, Nicolas and Karine Jacob and Noha Gerges and Barbara Hutter and Huriye Seker-Cin and Hendrik Witt and Alexandre Montpetit and S{\'e}bastien Brunet and Pierre Lepage and Genevi{\`e}ve Bourret and Almos Klekner and L{\'a}szl{\'o} Bogn{\'a}r and Peter Hauser and Mikl{\'o}s Garami and Farmer, {Jean Pierre} and Montes, {Jose Luis} and Jeffrey Atkinson and Sally Lambert and Tony Kwan and Andrey Korshunov and Uri Tabori and {Peter Collins}, V. and Steffen Albrecht and Damien Faury and Pfister, {Stefan M.} and Werner Paulus and Martin Hasselblatt and Jones, {David T.W.} and Nada Jabado",

year = "2015",

doi = "10.18632/oncotarget.5571",

language = "English",

volume = "6",

pages = "31844--31856",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

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Fontebasso, AM, Shirinian, M, Khuong-Quang, DA, Bechet, D, Gayden, T, Kool, M, De Jay, N, Jacob, K, Gerges, N, Hutter, B, Seker-Cin, H, Witt, H, Montpetit, A, Brunet, S, Lepage, P, Bourret, G, Klekner, A, Bognár, L, Hauser, P, Garami, M, Farmer, JP, Montes, JL, Atkinson, J, Lambert, S, Kwan, T, Korshunov, A, Tabori, U, Peter Collins, V, Albrecht, S, Faury, D, Pfister, SM, Paulus, W, Hasselblatt, M, Jones, DTW & Jabado, N 2015, 'Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age', Oncotarget, vol. 6, no. 31, pp. 31844-31856. https://doi.org/10.18632/oncotarget.5571

TY - JOUR

T1 - Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

AU - Fontebasso, Adam M.

AU - Shirinian, Margret

AU - Khuong-Quang, Dong Anh

AU - Bechet, Denise

AU - Gayden, Tenzin

AU - Kool, Marcel

AU - De Jay, Nicolas

AU - Jacob, Karine

AU - Gerges, Noha

AU - Hutter, Barbara

AU - Seker-Cin, Huriye

AU - Witt, Hendrik

AU - Montpetit, Alexandre

AU - Brunet, Sébastien

AU - Lepage, Pierre

AU - Bourret, Geneviève

AU - Klekner, Almos

AU - Bognár, László

AU - Hauser, Peter

AU - Garami, Miklós

AU - Farmer, Jean Pierre

AU - Montes, Jose Luis

AU - Atkinson, Jeffrey

AU - Lambert, Sally

AU - Kwan, Tony

AU - Korshunov, Andrey

AU - Tabori, Uri

AU - Peter Collins, V.

AU - Albrecht, Steffen

AU - Faury, Damien

AU - Pfister, Stefan M.

AU - Paulus, Werner

AU - Hasselblatt, Martin

AU - Jones, David T.W.

AU - Jabado, Nada

PY - 2015

Y1 - 2015

N2 - Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting noncerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2), whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.

AB - Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting noncerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2), whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.

KW - Aneuploidy

KW - BRAF

KW - MDM2

KW - Pilocytic astrocytoma

KW - PLK2

UR - http://www.scopus.com/inward/record.url?scp=84945563439&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.5571

DO - 10.18632/oncotarget.5571

M3 - Article

C2 - 26378811

AN - SCOPUS:84945563439

SN - 1949-2553

VL - 6

SP - 31844

EP - 31856

JO - Oncotarget

JF - Oncotarget

IS - 31

ER -

Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

Abstract

Keywords

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