A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants

0522862 - ÚMG 2020 RIV GB eng J - Journal Article
Tichá, I. - Hojný, J. - Michálková, R. - Kodet, O. - Krkavcová, E. - Hájková, N. - Nemejcova, K. - Bartu, M. - Jaksa, R. - Dura, M. - Kanwal, Madiha - Martiníková, Andra Stefania - Macůrek, Libor - Zemankova, P. - Kleibl, Z. - Dundr, P.
A comprehensive evaluation of pathogenic mutations in primary cutaneous melanomas, including the identification of novel loss-of-function variants.
Scientific Reports. Roč. 9, November (2019), č. článku 17050. ISSN 2045-2322. E-ISSN 2045-2322
R&D Projects: GA MŠMT(CZ) LM2015062
Institutional support: RVO:68378050
Keywords : ultraviolet-radiation * recurrent mutations * driver mutations * targeted therapy * p53 * classification * melanogenesis * expression * network * immunotherapy
OECD category: Oncology
Impact factor: 3.998, year: 2019
Method of publishing: Limited access
https://www.nature.com/articles/s41598-019-53636-x

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.
Permanent Link: http://hdl.handle.net/11104/0307282