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Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations

PURPOSE: Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more freq...

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Autores principales: Cosgarea, Ioana, Ugurel, Selma, Sucker, Antje, Livingstone, Elisabeth, Zimmer, Lisa, Ziemer, Mirjana, Utikal, Jochen, Mohr, Peter, Pfeiffer, Christiane, Pföhler, Claudia, Hillen, Uwe, Horn, Susanne, Schadendorf, Dirk, Griewank, Klaus G., Roesch, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522195/
https://www.ncbi.nlm.nih.gov/pubmed/28380455
http://dx.doi.org/10.18632/oncotarget.16542
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author Cosgarea, Ioana
Ugurel, Selma
Sucker, Antje
Livingstone, Elisabeth
Zimmer, Lisa
Ziemer, Mirjana
Utikal, Jochen
Mohr, Peter
Pfeiffer, Christiane
Pföhler, Claudia
Hillen, Uwe
Horn, Susanne
Schadendorf, Dirk
Griewank, Klaus G.
Roesch, Alexander
author_facet Cosgarea, Ioana
Ugurel, Selma
Sucker, Antje
Livingstone, Elisabeth
Zimmer, Lisa
Ziemer, Mirjana
Utikal, Jochen
Mohr, Peter
Pfeiffer, Christiane
Pföhler, Claudia
Hillen, Uwe
Horn, Susanne
Schadendorf, Dirk
Griewank, Klaus G.
Roesch, Alexander
author_sort Cosgarea, Ioana
collection PubMed
description PURPOSE: Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown. EXPERIMENTAL DESIGN AND RESULTS: In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples. CONCLUSIONS: Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors.
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spelling pubmed-55221952017-08-21 Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations Cosgarea, Ioana Ugurel, Selma Sucker, Antje Livingstone, Elisabeth Zimmer, Lisa Ziemer, Mirjana Utikal, Jochen Mohr, Peter Pfeiffer, Christiane Pföhler, Claudia Hillen, Uwe Horn, Susanne Schadendorf, Dirk Griewank, Klaus G. Roesch, Alexander Oncotarget Research Paper PURPOSE: Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown. EXPERIMENTAL DESIGN AND RESULTS: In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples. CONCLUSIONS: Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors. Impact Journals LLC 2017-03-24 /pmc/articles/PMC5522195/ /pubmed/28380455 http://dx.doi.org/10.18632/oncotarget.16542 Text en Copyright: © 2017 Cosgarea et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cosgarea, Ioana
Ugurel, Selma
Sucker, Antje
Livingstone, Elisabeth
Zimmer, Lisa
Ziemer, Mirjana
Utikal, Jochen
Mohr, Peter
Pfeiffer, Christiane
Pföhler, Claudia
Hillen, Uwe
Horn, Susanne
Schadendorf, Dirk
Griewank, Klaus G.
Roesch, Alexander
Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations
title Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations
title_full Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations
title_fullStr Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations
title_full_unstemmed Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations
title_short Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations
title_sort targeted next generation sequencing of mucosal melanomas identifies frequent nf1 and ras mutations
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522195/
https://www.ncbi.nlm.nih.gov/pubmed/28380455
http://dx.doi.org/10.18632/oncotarget.16542
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