Exomic sequencing of four rare central nervous system tumor types

Chetan Bettegowda; Nishant Agrawal; Yuchen Jiao; Yuxuan Wang; Laura D. Wood; Fausto J Rodriguez; Ralph H. Hruban; Gary L. Gallia; Zev A. Binder; Callen J. Riggins; Vafi Salmasi; Gregory J. Riggins; Zachary J. Reitman; Ahmed Rasheed; Stephen Keir; Sueli Shinjo; Suely Marie; Roger McLendon; George Jallo; Bert Vogelstein; Darell Bigner; Hai Yan; Kenneth W. Kinzler; Nickolas Papadopoulos

doi:10.18632/oncotarget.964

Exomic sequencing of four rare central nervous system tumor types

Chetan Bettegowda, Nishant Agrawal, Yuchen Jiao, Yuxuan Wang, Laura D. Wood, Fausto J Rodriguez, Ralph H. Hruban, Gary L. Gallia, Zev A. Binder, Callen J. Riggins, Vafi Salmasi, Gregory J. Riggins, Zachary J. Reitman, Ahmed Rasheed, Stephen Keir, Sueli Shinjo, Suely Marie, Roger McLendon, George Jallo, Bert VogelsteinDarell Bigner, Hai Yan, Kenneth W. Kinzler, Nickolas Papadopoulos

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52 Scopus citations

Abstract

A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.

Original language	English (US)
Pages (from-to)	572-583
Number of pages	12
Journal	Oncotarget
Volume	4
Issue number	4
DOIs	https://doi.org/10.18632/oncotarget.964
State	Published - Apr 2013

Keywords

Brain tumors
Cancer genetics
Central nervous system (CNS) tumors
Exome sequencing
Pediatric tumors

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.964

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Bettegowda, C., Agrawal, N., Jiao, Y., Wang, Y., Wood, L. D., Rodriguez, F. J., Hruban, R. H., Gallia, G. L., Binder, Z. A., Riggins, C. J., Salmasi, V., Riggins, G. J., Reitman, Z. J., Rasheed, A., Keir, S., Shinjo, S., Marie, S., McLendon, R., Jallo, G., ... Papadopoulos, N. (2013). Exomic sequencing of four rare central nervous system tumor types. Oncotarget, 4(4), 572-583. https://doi.org/10.18632/oncotarget.964

Bettegowda, C, Agrawal, N, Jiao, Y, Wang, Y , Wood, LD, Rodriguez, FJ, Hruban, RH , Gallia, GL, Binder, ZA, Riggins, CJ, Salmasi, V, Riggins, GJ, Reitman, ZJ, Rasheed, A, Keir, S, Shinjo, S, Marie, S, McLendon, R, Jallo, G , Vogelstein, B, Bigner, D, Yan, H, Kinzler, KW & Papadopoulos, N 2013, 'Exomic sequencing of four rare central nervous system tumor types', Oncotarget, vol. 4, no. 4, pp. 572-583. https://doi.org/10.18632/oncotarget.964

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abstract = "A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.",

keywords = "Brain tumors, Cancer genetics, Central nervous system (CNS) tumors, Exome sequencing, Pediatric tumors",

author = "Chetan Bettegowda and Nishant Agrawal and Yuchen Jiao and Yuxuan Wang and Wood, {Laura D.} and Rodriguez, {Fausto J} and Hruban, {Ralph H.} and Gallia, {Gary L.} and Binder, {Zev A.} and Riggins, {Callen J.} and Vafi Salmasi and Riggins, {Gregory J.} and Reitman, {Zachary J.} and Ahmed Rasheed and Stephen Keir and Sueli Shinjo and Suely Marie and Roger McLendon and George Jallo and Bert Vogelstein and Darell Bigner and Hai Yan and Kinzler, {Kenneth W.} and Nickolas Papadopoulos",

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AU - Bettegowda, Chetan

AU - Agrawal, Nishant

AU - Jiao, Yuchen

AU - Wang, Yuxuan

AU - Wood, Laura D.

AU - Rodriguez, Fausto J

AU - Hruban, Ralph H.

AU - Gallia, Gary L.

AU - Binder, Zev A.

AU - Riggins, Callen J.

AU - Salmasi, Vafi

AU - Riggins, Gregory J.

AU - Reitman, Zachary J.

AU - Rasheed, Ahmed

AU - Keir, Stephen

AU - Shinjo, Sueli

AU - Marie, Suely

AU - McLendon, Roger

AU - Jallo, George

AU - Vogelstein, Bert

AU - Bigner, Darell

AU - Yan, Hai

AU - Kinzler, Kenneth W.

AU - Papadopoulos, Nickolas

PY - 2013/4

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N2 - A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.

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Exomic sequencing of four rare central nervous system tumor types

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