A biobank of patient-derived pediatric brain tumor models

Sebastian Brabetz; Sarah E.S. Leary; Susanne N. Gröbner; Madison W. Nakamoto; Huriye Şeker-Cin; Emily J. Girard; Bonnie Cole; Andrew D. Strand; Karina L. Bloom; Volker Hovestadt; Norman L. Mack; Fiona Pakiam; Benjamin Schwalm; Andrey Korshunov; Gnana Prakash Balasubramanian; Paul A. Northcott; Kyle D. Pedro; Joyoti Dey; Stacey Hansen; Sally Ditzler; Peter Lichter; Lukas Chavez; David T.W. Jones; Jan Koster; Stefan M. Pfister; Marcel Kool; James M. Olson

doi:10.1038/s41591-018-0207-3

A biobank of patient-derived pediatric brain tumor models

Sebastian Brabetz, Sarah E.S. Leary, Susanne N. Gröbner, Madison W. Nakamoto, Huriye Şeker-Cin, Emily J. Girard, Bonnie Cole, Andrew D. Strand, Karina L. Bloom, Volker Hovestadt, Norman L. Mack, Fiona Pakiam, Benjamin Schwalm, Andrey Korshunov, Gnana Prakash Balasubramanian, Paul A. Northcott, Kyle D. Pedro, Joyoti Dey, Stacey Hansen, Sally DitzlerPeter Lichter, Lukas Chavez, David T.W. Jones, Jan Koster, Stefan M. Pfister, Marcel Kool, James M. Olson

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.

Originele taal-2	Engels
Pagina's (van-tot)	1752-1761
Aantal pagina's	10
Tijdschrift	Nature Medicine
Volume	24
Nummer van het tijdschrift	11
DOI's	https://doi.org/10.1038/s41591-018-0207-3
Status	Gepubliceerd - 1 nov. 2018
Extern gepubliceerd	Ja

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Brabetz, S., Leary, S. E. S., Gröbner, S. N., Nakamoto, M. W., Şeker-Cin, H., Girard, E. J., Cole, B., Strand, A. D., Bloom, K. L., Hovestadt, V., Mack, N. L., Pakiam, F., Schwalm, B., Korshunov, A., Balasubramanian, G. P., Northcott, P. A., Pedro, K. D., Dey, J., Hansen, S., ... Olson, J. M. (2018). A biobank of patient-derived pediatric brain tumor models. Nature Medicine, 24(11), 1752-1761. https://doi.org/10.1038/s41591-018-0207-3

@article{98f297614e0c44cc9267b283f2d22180,

title = "A biobank of patient-derived pediatric brain tumor models",

abstract = "Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children{\textquoteright}s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.",

author = "Sebastian Brabetz and Leary, {Sarah E.S.} and Gr{\"o}bner, {Susanne N.} and Nakamoto, {Madison W.} and Huriye {\c S}eker-Cin and Girard, {Emily J.} and Bonnie Cole and Strand, {Andrew D.} and Bloom, {Karina L.} and Volker Hovestadt and Mack, {Norman L.} and Fiona Pakiam and Benjamin Schwalm and Andrey Korshunov and Balasubramanian, {Gnana Prakash} and Northcott, {Paul A.} and Pedro, {Kyle D.} and Joyoti Dey and Stacey Hansen and Sally Ditzler and Peter Lichter and Lukas Chavez and Jones, {David T.W.} and Jan Koster and Pfister, {Stefan M.} and Marcel Kool and Olson, {James M.}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2018",

month = nov,

day = "1",

doi = "10.1038/s41591-018-0207-3",

language = "English",

volume = "24",

pages = "1752--1761",

journal = "Nature Medicine",

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Brabetz, S, Leary, SES, Gröbner, SN, Nakamoto, MW, Şeker-Cin, H, Girard, EJ, Cole, B, Strand, AD, Bloom, KL, Hovestadt, V, Mack, NL, Pakiam, F, Schwalm, B, Korshunov, A, Balasubramanian, GP, Northcott, PA, Pedro, KD, Dey, J, Hansen, S, Ditzler, S, Lichter, P, Chavez, L, Jones, DTW, Koster, J, Pfister, SM, Kool, M & Olson, JM 2018, 'A biobank of patient-derived pediatric brain tumor models', Nature Medicine, vol. 24, nr. 11, blz. 1752-1761. https://doi.org/10.1038/s41591-018-0207-3

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AU - Brabetz, Sebastian

AU - Leary, Sarah E.S.

AU - Gröbner, Susanne N.

AU - Nakamoto, Madison W.

AU - Şeker-Cin, Huriye

AU - Girard, Emily J.

AU - Cole, Bonnie

AU - Strand, Andrew D.

AU - Bloom, Karina L.

AU - Hovestadt, Volker

AU - Mack, Norman L.

AU - Pakiam, Fiona

AU - Schwalm, Benjamin

AU - Korshunov, Andrey

AU - Balasubramanian, Gnana Prakash

AU - Northcott, Paul A.

AU - Pedro, Kyle D.

AU - Dey, Joyoti

AU - Hansen, Stacey

AU - Ditzler, Sally

AU - Lichter, Peter

AU - Chavez, Lukas

AU - Jones, David T.W.

AU - Koster, Jan

AU - Pfister, Stefan M.

AU - Kool, Marcel

AU - Olson, James M.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.

AB - Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.

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DO - 10.1038/s41591-018-0207-3

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AN - SCOPUS:85055262681

SN - 1078-8956

VL - 24

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EP - 1761

JO - Nature Medicine

JF - Nature Medicine

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ER -

A biobank of patient-derived pediatric brain tumor models

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