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Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model

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Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model. / Niesen, Judith; Ohli, Jasmin; Sedlacik, Jan; Dührsen, Lasse; Hellwig, Malte; Spohn, Michael; Holsten, Till; Schüller, Ulrich.

In: CANCER LETT, Vol. 477, 01.05.2020, p. 10-18.

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

Harvard

Niesen, J, Ohli, J, Sedlacik, J, Dührsen, L, Hellwig, M, Spohn, M, Holsten, T & Schüller, U 2020, 'Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model', CANCER LETT, vol. 477, pp. 10-18. https://doi.org/10.1016/j.canlet.2020.02.028

APA

Niesen, J., Ohli, J., Sedlacik, J., Dührsen, L., Hellwig, M., Spohn, M., Holsten, T., & Schüller, U. (2020). Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model. CANCER LETT, 477, 10-18. https://doi.org/10.1016/j.canlet.2020.02.028

Vancouver

Niesen J, Ohli J, Sedlacik J, Dührsen L, Hellwig M, Spohn M et al. Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model. CANCER LETT. 2020 May 1;477:10-18. https://doi.org/10.1016/j.canlet.2020.02.028

Bibtex

@article{bb9df890a02942ceac9c094fe7f1a1cd,
title = "Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model",
abstract = "Medulloblastoma (MB) is the most frequent malignant brain tumour in children with a poor outcome. Divided into four molecular subgroups, MB of the Sonic hedgehog (SHH) subgroup accounts for approximately 25% of the cases and is driven by mutations within components of the SHH pathway, such as its receptors PTCH1 or SMO. A fraction of these cases additionally harbour PIK3CA mutations, the relevance of which is so far unknown. To unravel the role of Pik3ca mutations alone or in combination with a constitutively activated SHH signalling pathway, transgenic mice were used. These mice show mutated variants within Smo, Ptch1 or Pik3ca genes in cerebellar granule neuron precursors, which represent the cellular origin of SHH MB. Our results show that Pik3ca mutations alone are insufficient to cause developmental alterations or to initiate MB. However, they significantly accelerate the growth of Shh MB, induce tumour spread throughout the cerebrospinal fluid, and result in lower survival rates of mice with a double Pik3caH1047R/SmoM2 or Pik3caH1047R/Ptch1 mutation. Therefore, PIK3CA mutations in SHH MB may represent a therapeutic target for first and second line combination treatments.",
author = "Judith Niesen and Jasmin Ohli and Jan Sedlacik and Lasse D{\"u}hrsen and Malte Hellwig and Michael Spohn and Till Holsten and Ulrich Sch{\"u}ller",
note = "Copyright {\textcopyright} 2020 Elsevier B.V. All rights reserved.",
year = "2020",
month = may,
day = "1",
doi = "10.1016/j.canlet.2020.02.028",
language = "English",
volume = "477",
pages = "10--18",
journal = "CANCER LETT",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Pik3ca mutations significantly enhance the growth of Shh medulloblastoma and lead to metastatic tumour growth in a novel mouse model

AU - Niesen, Judith

AU - Ohli, Jasmin

AU - Sedlacik, Jan

AU - Dührsen, Lasse

AU - Hellwig, Malte

AU - Spohn, Michael

AU - Holsten, Till

AU - Schüller, Ulrich

N1 - Copyright © 2020 Elsevier B.V. All rights reserved.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Medulloblastoma (MB) is the most frequent malignant brain tumour in children with a poor outcome. Divided into four molecular subgroups, MB of the Sonic hedgehog (SHH) subgroup accounts for approximately 25% of the cases and is driven by mutations within components of the SHH pathway, such as its receptors PTCH1 or SMO. A fraction of these cases additionally harbour PIK3CA mutations, the relevance of which is so far unknown. To unravel the role of Pik3ca mutations alone or in combination with a constitutively activated SHH signalling pathway, transgenic mice were used. These mice show mutated variants within Smo, Ptch1 or Pik3ca genes in cerebellar granule neuron precursors, which represent the cellular origin of SHH MB. Our results show that Pik3ca mutations alone are insufficient to cause developmental alterations or to initiate MB. However, they significantly accelerate the growth of Shh MB, induce tumour spread throughout the cerebrospinal fluid, and result in lower survival rates of mice with a double Pik3caH1047R/SmoM2 or Pik3caH1047R/Ptch1 mutation. Therefore, PIK3CA mutations in SHH MB may represent a therapeutic target for first and second line combination treatments.

AB - Medulloblastoma (MB) is the most frequent malignant brain tumour in children with a poor outcome. Divided into four molecular subgroups, MB of the Sonic hedgehog (SHH) subgroup accounts for approximately 25% of the cases and is driven by mutations within components of the SHH pathway, such as its receptors PTCH1 or SMO. A fraction of these cases additionally harbour PIK3CA mutations, the relevance of which is so far unknown. To unravel the role of Pik3ca mutations alone or in combination with a constitutively activated SHH signalling pathway, transgenic mice were used. These mice show mutated variants within Smo, Ptch1 or Pik3ca genes in cerebellar granule neuron precursors, which represent the cellular origin of SHH MB. Our results show that Pik3ca mutations alone are insufficient to cause developmental alterations or to initiate MB. However, they significantly accelerate the growth of Shh MB, induce tumour spread throughout the cerebrospinal fluid, and result in lower survival rates of mice with a double Pik3caH1047R/SmoM2 or Pik3caH1047R/Ptch1 mutation. Therefore, PIK3CA mutations in SHH MB may represent a therapeutic target for first and second line combination treatments.

U2 - 10.1016/j.canlet.2020.02.028

DO - 10.1016/j.canlet.2020.02.028

M3 - SCORING: Journal article

C2 - 32112900

VL - 477

SP - 10

EP - 18

JO - CANCER LETT

JF - CANCER LETT

SN - 0304-3835

ER -