A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma

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A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma. / Yde, Christina Westmose; Sehested, Astrid; Regué, Àngels Mateu; Østrup, Olga; Scheie, David; Nysom, Karsten; Nielsen, Finn Cilius; Rossing, Maria.

I: Cancer genetics and cytogenetics, Bind 209, Nr. 10, 10.2016, s. 440-444.

Publikation: Bidrag til tidsskriftLetterfagfællebedømt

Harvard

Yde, CW, Sehested, A, Regué, ÀM, Østrup, O, Scheie, D, Nysom, K, Nielsen, FC & Rossing, M 2016, 'A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma', Cancer genetics and cytogenetics, bind 209, nr. 10, s. 440-444. https://doi.org/10.1016/j.cancergen.2016.09.002

APA

Yde, C. W., Sehested, A., Regué, À. M., Østrup, O., Scheie, D., Nysom, K., Nielsen, F. C., & Rossing, M. (2016). A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma. Cancer genetics and cytogenetics, 209(10), 440-444. https://doi.org/10.1016/j.cancergen.2016.09.002

Vancouver

Yde CW, Sehested A, Regué ÀM, Østrup O, Scheie D, Nysom K o.a. A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma. Cancer genetics and cytogenetics. 2016 okt.;209(10):440-444. https://doi.org/10.1016/j.cancergen.2016.09.002

Author

Yde, Christina Westmose ; Sehested, Astrid ; Regué, Àngels Mateu ; Østrup, Olga ; Scheie, David ; Nysom, Karsten ; Nielsen, Finn Cilius ; Rossing, Maria. / A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma. I: Cancer genetics and cytogenetics. 2016 ; Bind 209, Nr. 10. s. 440-444.

Bibtex

@article{351c5fb131cc4416b092f107785b222e,
title = "A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma",
abstract = "Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA. The novel fusion was identified as part of a comprehensive genomic tumor profiling. We show that the NFIA:RAF1 fusion results in constitutive Raf1 kinase activity, leading to activation of downstream MEK1/2 cascade and increased proliferation of cancer cells. The NFIA:RAF1 fusion displayed distinct subcellular localization towards the plasma membrane indicative of Raf-1 activation, in contrast to both wild type NFIA and Raf-1, which were localized in the nucleus and cytoplasm, respectively. In conclusion, our data support the existence of rare oncogenic RAF1 fusions with constitutive Raf-1 activity. This highlights the need for broad genetic testing in order to refine diagnostics of PA and to unravel potential treatment options, e.g. with MEK inhibitors.",
keywords = "Journal Article",
author = "Yde, {Christina Westmose} and Astrid Sehested and Regu{\'e}, {{\`A}ngels Mateu} and Olga {\O}strup and David Scheie and Karsten Nysom and Nielsen, {Finn Cilius} and Maria Rossing",
note = "Copyright {\textcopyright} 2016 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = oct,
doi = "10.1016/j.cancergen.2016.09.002",
language = "English",
volume = "209",
pages = "440--444",
journal = "Cancer genetics and cytogenetics",
issn = "0165-4608",
publisher = "Elsevier",
number = "10",

}

RIS

TY - JOUR

T1 - A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma

AU - Yde, Christina Westmose

AU - Sehested, Astrid

AU - Regué, Àngels Mateu

AU - Østrup, Olga

AU - Scheie, David

AU - Nysom, Karsten

AU - Nielsen, Finn Cilius

AU - Rossing, Maria

N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2016/10

Y1 - 2016/10

N2 - Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA. The novel fusion was identified as part of a comprehensive genomic tumor profiling. We show that the NFIA:RAF1 fusion results in constitutive Raf1 kinase activity, leading to activation of downstream MEK1/2 cascade and increased proliferation of cancer cells. The NFIA:RAF1 fusion displayed distinct subcellular localization towards the plasma membrane indicative of Raf-1 activation, in contrast to both wild type NFIA and Raf-1, which were localized in the nucleus and cytoplasm, respectively. In conclusion, our data support the existence of rare oncogenic RAF1 fusions with constitutive Raf-1 activity. This highlights the need for broad genetic testing in order to refine diagnostics of PA and to unravel potential treatment options, e.g. with MEK inhibitors.

AB - Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA. The novel fusion was identified as part of a comprehensive genomic tumor profiling. We show that the NFIA:RAF1 fusion results in constitutive Raf1 kinase activity, leading to activation of downstream MEK1/2 cascade and increased proliferation of cancer cells. The NFIA:RAF1 fusion displayed distinct subcellular localization towards the plasma membrane indicative of Raf-1 activation, in contrast to both wild type NFIA and Raf-1, which were localized in the nucleus and cytoplasm, respectively. In conclusion, our data support the existence of rare oncogenic RAF1 fusions with constitutive Raf-1 activity. This highlights the need for broad genetic testing in order to refine diagnostics of PA and to unravel potential treatment options, e.g. with MEK inhibitors.

KW - Journal Article

U2 - 10.1016/j.cancergen.2016.09.002

DO - 10.1016/j.cancergen.2016.09.002

M3 - Letter

C2 - 27810072

VL - 209

SP - 440

EP - 444

JO - Cancer genetics and cytogenetics

JF - Cancer genetics and cytogenetics

SN - 0165-4608

IS - 10

ER -

ID: 176010474