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Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts

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Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts. / Pöschl, Julia; Stark, Sebastian; Neumann, Philipp; Gröbner, Susanne; Kawauchi, Daisuke; Jones, David T W; Northcott, Paul A; Lichter, Peter; Pfister, Stefan M; Kool, Marcel; Schüller, Ulrich.

In: ACTA NEUROPATHOL, Vol. 128, No. 1, 07.2014, p. 123-36.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Pöschl, J, Stark, S, Neumann, P, Gröbner, S, Kawauchi, D, Jones, DTW, Northcott, PA, Lichter, P, Pfister, SM, Kool, M & Schüller, U 2014, 'Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts', ACTA NEUROPATHOL, vol. 128, no. 1, pp. 123-36. https://doi.org/10.1007/s00401-014-1297-8

APA

Pöschl, J., Stark, S., Neumann, P., Gröbner, S., Kawauchi, D., Jones, D. T. W., Northcott, P. A., Lichter, P., Pfister, S. M., Kool, M., & Schüller, U. (2014). Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts. ACTA NEUROPATHOL, 128(1), 123-36. https://doi.org/10.1007/s00401-014-1297-8

Vancouver

Pöschl J, Stark S, Neumann P, Gröbner S, Kawauchi D, Jones DTW et al. Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts. ACTA NEUROPATHOL. 2014 Jul;128(1):123-36. https://doi.org/10.1007/s00401-014-1297-8

Bibtex

@article{c375db93119940ada18c9bc5a0efdd4a,
title = "Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts",
abstract = "Medulloblastoma is a malignant embryonal brain tumor with highly variable outcome. In order to study the biology of this tumor and to perform preclinical treatment studies, a lot of effort has been put into the generation of appropriate mouse models. The usage of these models, however, has become debatable with the advances in human medulloblastoma subgrouping. This study brings together multiple relevant mouse models and matches genetic alterations and gene expression data of 140 murine tumors with 423 human medulloblastomas in a global way. Using AGDEX analysis and k-means clustering, we show that the Blbp-cre::Ctnnb1(ex3)(Fl/+)Trp53 (Fl/Fl) mouse model fits well to human WNT medulloblastoma, and that, among various Myc- or Mycn-based mouse medulloblastomas, tumors in Glt1-tTA::TRE-MYCN/Luc mice proved to be most specific for human group 3 medulloblastoma. None of the analyzed models displayed a significant match to group 4 tumors. Intriguingly, mice with Ptch1 or Smo mutations selectively modeled SHH medulloblastomas of adulthood, although such mutations occur in all human age groups. We therefore suggest that the infantile or adult gene expression pattern of SHH MBs are not solely determined by specific mutations. This is supported by the observation that human medulloblastomas with PTCH1 mutations displayed more similarities to PTCH1 wild-type tumors of the same age group than to PTCH1-mutated tumors of the other age group. Together, we provide novel insights into previously unrecognized specificity of distinct models and suggest these findings as a solid basis to choose the appropriate model for preclinical studies on medulloblastoma.",
keywords = "Adult, Age Factors, Animals, Brain, Brain Neoplasms, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomics, Hedgehog Proteins, Humans, Infant, Medulloblastoma, Mice, Mice, Transgenic, Mutation, Polymorphism, Single Nucleotide, Receptors, Cell Surface, Signal Transduction, Transcriptome, Journal Article, Research Support, Non-U.S. Gov't",
author = "Julia P{\"o}schl and Sebastian Stark and Philipp Neumann and Susanne Gr{\"o}bner and Daisuke Kawauchi and Jones, {David T W} and Northcott, {Paul A} and Peter Lichter and Pfister, {Stefan M} and Marcel Kool and Ulrich Sch{\"u}ller",
year = "2014",
month = jul,
doi = "10.1007/s00401-014-1297-8",
language = "English",
volume = "128",
pages = "123--36",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts

AU - Pöschl, Julia

AU - Stark, Sebastian

AU - Neumann, Philipp

AU - Gröbner, Susanne

AU - Kawauchi, Daisuke

AU - Jones, David T W

AU - Northcott, Paul A

AU - Lichter, Peter

AU - Pfister, Stefan M

AU - Kool, Marcel

AU - Schüller, Ulrich

PY - 2014/7

Y1 - 2014/7

N2 - Medulloblastoma is a malignant embryonal brain tumor with highly variable outcome. In order to study the biology of this tumor and to perform preclinical treatment studies, a lot of effort has been put into the generation of appropriate mouse models. The usage of these models, however, has become debatable with the advances in human medulloblastoma subgrouping. This study brings together multiple relevant mouse models and matches genetic alterations and gene expression data of 140 murine tumors with 423 human medulloblastomas in a global way. Using AGDEX analysis and k-means clustering, we show that the Blbp-cre::Ctnnb1(ex3)(Fl/+)Trp53 (Fl/Fl) mouse model fits well to human WNT medulloblastoma, and that, among various Myc- or Mycn-based mouse medulloblastomas, tumors in Glt1-tTA::TRE-MYCN/Luc mice proved to be most specific for human group 3 medulloblastoma. None of the analyzed models displayed a significant match to group 4 tumors. Intriguingly, mice with Ptch1 or Smo mutations selectively modeled SHH medulloblastomas of adulthood, although such mutations occur in all human age groups. We therefore suggest that the infantile or adult gene expression pattern of SHH MBs are not solely determined by specific mutations. This is supported by the observation that human medulloblastomas with PTCH1 mutations displayed more similarities to PTCH1 wild-type tumors of the same age group than to PTCH1-mutated tumors of the other age group. Together, we provide novel insights into previously unrecognized specificity of distinct models and suggest these findings as a solid basis to choose the appropriate model for preclinical studies on medulloblastoma.

AB - Medulloblastoma is a malignant embryonal brain tumor with highly variable outcome. In order to study the biology of this tumor and to perform preclinical treatment studies, a lot of effort has been put into the generation of appropriate mouse models. The usage of these models, however, has become debatable with the advances in human medulloblastoma subgrouping. This study brings together multiple relevant mouse models and matches genetic alterations and gene expression data of 140 murine tumors with 423 human medulloblastomas in a global way. Using AGDEX analysis and k-means clustering, we show that the Blbp-cre::Ctnnb1(ex3)(Fl/+)Trp53 (Fl/Fl) mouse model fits well to human WNT medulloblastoma, and that, among various Myc- or Mycn-based mouse medulloblastomas, tumors in Glt1-tTA::TRE-MYCN/Luc mice proved to be most specific for human group 3 medulloblastoma. None of the analyzed models displayed a significant match to group 4 tumors. Intriguingly, mice with Ptch1 or Smo mutations selectively modeled SHH medulloblastomas of adulthood, although such mutations occur in all human age groups. We therefore suggest that the infantile or adult gene expression pattern of SHH MBs are not solely determined by specific mutations. This is supported by the observation that human medulloblastomas with PTCH1 mutations displayed more similarities to PTCH1 wild-type tumors of the same age group than to PTCH1-mutated tumors of the other age group. Together, we provide novel insights into previously unrecognized specificity of distinct models and suggest these findings as a solid basis to choose the appropriate model for preclinical studies on medulloblastoma.

KW - Adult

KW - Age Factors

KW - Animals

KW - Brain

KW - Brain Neoplasms

KW - Disease Models, Animal

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Genomics

KW - Hedgehog Proteins

KW - Humans

KW - Infant

KW - Medulloblastoma

KW - Mice

KW - Mice, Transgenic

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Receptors, Cell Surface

KW - Signal Transduction

KW - Transcriptome

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00401-014-1297-8

DO - 10.1007/s00401-014-1297-8

M3 - SCORING: Journal article

C2 - 24871706

VL - 128

SP - 123

EP - 136

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 1

ER -