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Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing

Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4–8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This int...

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Autores principales: Pupo, Gulietta M., Boyd, Suzanah C., Fung, Carina, Carlino, Matteo S., Menzies, Alexander M., Pedersen, Bernadette, Johansson, Peter, Hayward, Nicholas K., Kefford, Richard F., Scolyer, Richard A., Long, Georgina V., Rizos, Helen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426037/
https://www.ncbi.nlm.nih.gov/pubmed/28503307
http://dx.doi.org/10.1186/s40364-017-0098-3
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author Pupo, Gulietta M.
Boyd, Suzanah C.
Fung, Carina
Carlino, Matteo S.
Menzies, Alexander M.
Pedersen, Bernadette
Johansson, Peter
Hayward, Nicholas K.
Kefford, Richard F.
Scolyer, Richard A.
Long, Georgina V.
Rizos, Helen
author_facet Pupo, Gulietta M.
Boyd, Suzanah C.
Fung, Carina
Carlino, Matteo S.
Menzies, Alexander M.
Pedersen, Bernadette
Johansson, Peter
Hayward, Nicholas K.
Kefford, Richard F.
Scolyer, Richard A.
Long, Georgina V.
Rizos, Helen
author_sort Pupo, Gulietta M.
collection PubMed
description Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4–8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo. Herein we demonstrate that in three melanomas biopsied from patients with acquired resistance to BRAF inhibitors, alternate BRAF exon 4–8 splicing is not associated with this intronic branch point mutation. We also confirm that melanoma cells expressing BRAF splicing variants retain exquisite sensitivity to existing FDA-approved MEK inhibitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-017-0098-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-54260372017-05-12 Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing Pupo, Gulietta M. Boyd, Suzanah C. Fung, Carina Carlino, Matteo S. Menzies, Alexander M. Pedersen, Bernadette Johansson, Peter Hayward, Nicholas K. Kefford, Richard F. Scolyer, Richard A. Long, Georgina V. Rizos, Helen Biomark Res Short Report Alternate BRAF splicing is the most common mechanism of acquired resistance to BRAF inhibitor treatment in melanoma. Recently, alternate BRAF exon 4–8 splicing was shown to involve an intronic mutation, located 51 nucleotides upstream of BRAF exon 9 within a predicted splicing branch point. This intronic mutation was identified in a single cell line but has not been examined in vivo. Herein we demonstrate that in three melanomas biopsied from patients with acquired resistance to BRAF inhibitors, alternate BRAF exon 4–8 splicing is not associated with this intronic branch point mutation. We also confirm that melanoma cells expressing BRAF splicing variants retain exquisite sensitivity to existing FDA-approved MEK inhibitors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-017-0098-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-11 /pmc/articles/PMC5426037/ /pubmed/28503307 http://dx.doi.org/10.1186/s40364-017-0098-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Pupo, Gulietta M.
Boyd, Suzanah C.
Fung, Carina
Carlino, Matteo S.
Menzies, Alexander M.
Pedersen, Bernadette
Johansson, Peter
Hayward, Nicholas K.
Kefford, Richard F.
Scolyer, Richard A.
Long, Georgina V.
Rizos, Helen
Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing
title Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing
title_full Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing
title_fullStr Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing
title_full_unstemmed Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing
title_short Clinical significance of intronic variants in BRAF inhibitor resistant melanomas with altered BRAF transcript splicing
title_sort clinical significance of intronic variants in braf inhibitor resistant melanomas with altered braf transcript splicing
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426037/
https://www.ncbi.nlm.nih.gov/pubmed/28503307
http://dx.doi.org/10.1186/s40364-017-0098-3
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