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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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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. |
format | Online Article Text |
id | pubmed-5426037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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