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A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants
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SYSNO ASEP 0522862 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants Author(s) Tichá, I. (CZ)
Hojný, J. (CZ)
Michálková, R. (CZ)
Kodet, O. (CZ)
Krkavcová, E. (CZ)
Hájková, N. (CZ)
Nemejcova, K. (CZ)
Bartu, M. (CZ)
Jaksa, R. (CZ)
Dura, M. (CZ)
Kanwal, Madiha (UMG-J)
Martiníková, Andra Stefania (UMG-J)
Macůrek, Libor (UMG-J) RID, ORCID
Zemankova, P. (CZ)
Kleibl, Z. (CZ)
Dundr, P. (CZ)Number of authors 16 Article number 17050 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 9, November (2019)Number of pages 15 s. Publication form Online - E Language eng - English Country GB - United Kingdom Keywords ultraviolet-radiation ; recurrent mutations ; driver mutations ; targeted therapy ; p53 ; classification ; melanogenesis ; expression ; network ; immunotherapy Subject RIV EB - Genetics ; Molecular Biology OECD category Oncology R&D Projects LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UMG-J - RVO:68378050 UT WOS 000497701800007 DOI 10.1038/s41598-019-53636-x Annotation The most common histological subtypes of cutaneous melanoma include superficial spreading and nodular melanoma. However, the spectrum of somatic mutations developed in those lesions and all potential druggable targets have not yet been fully elucidated. We present the results of a sequence capture NGS analysis of 114 primary nodular and superficial spreading melanomas identifying driver mutations using biostatistical, immunohistochemical and/or functional approach. The spectrum and frequency of pathogenic or likely pathogenic variants were identified across 54 evaluated genes, including 59 novel mutations, and the newly identified TP53 loss-of-function mutations p.(L194P) and p.(R280K). Frequently mutated genes most commonly affected the MAPK pathway, followed by chromatin remodeling, and cell cycle regulation. Frequent aberrations were also detected in the genes coding for proteins involved in DNA repair and the regulation and modification of cellular tight junctions. Furthermore, relatively frequent mutations were described in KDR and MET, which represent potential clinically important targets. Those results suggest that with the development of new therapeutic possibilities, not only BRAF testing, but complex molecular testing of cutaneous melanoma may become an integral part of the decision process concerning the treatment of patients with melanoma. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2020 Electronic address https://www.nature.com/articles/s41598-019-53636-x
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