DNA repair-based classification of melanoma cell lines reveals an effect of mutations in BRAF and NRAS driver genes on DNA repair capacity

Sauvaigo, Sylvie; Benkhiat, Manel; Braisaz, Florian; Libert, Sarah; Girard, Julien; Mouret, Stéphane; Fraipont, Florence de; Aspord, Caroline; Bouquet, Fanny; Leccia, M.-T.

doi:10.1101/2020.04.29.067900

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…Understanding how NRAS-and BRAF-mutant melanocytes respond to UVB damage will likely offer insight into the differential SNV burden observed here. Genotype-dependent DNA-damage responses were recently reported in melanoma cell lines (Sauvaigo et al 2020). However, an earlier report saw no correlation between repair capacity and melanoma genotype (Gaddameedhi et al 2010).…”

Section: Discussionmentioning

confidence: 96%

UVB mutagenesis differs in NRAS- and BRAF-mutant mouse models of melanoma

Bowman

Hennessey

Tallman

et al. 2019

Preprint

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It is difficult to discern the relative contributions of ultraviolet-A (UVA; 320-400nm) and ultraviolet-B (UVB; 280-320nm) radiation to human melanoma development. Here, we compared the tumorigenic consequences of a single UVA or UVB exposure in mouse models predisposed to Braf- or Nras-mutant melanoma. Exposures approximated the amount of UVA or UVB energy contained in ∼40 minutes of summer sunlight. While UVA accelerated melanoma onset in a subset of mice, UVB universally reduced tumor latency and induced gene mutations relevant to the human disease. Genomic analyses uncovered distinct mutational signatures specific to each UV spectrum. The UVB-specific signature was biased for mutations on the untranscribed DNA strand and closely mirrored mutational signatures enriched in human cutaneous melanoma. The UVA-specific signature mimicked SBS51, a mutational signature found in human uveal melanoma. Distinctions in the trinucleotide patterns of the UVA and UVB signatures suggest that cytosine deamination plays a key role in UVB-mediated melanomagenesis.

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Section: Discussionmentioning

confidence: 96%

UVB mutagenesis differs in NRAS- and BRAF-mutant mouse models of melanoma

Bowman

Hennessey

Tallman

et al. 2019

Preprint

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“…Another possibility is that Braf-mutant melanocytes are less efficient at resolving UVB-induced DNA lesions. Genotype-dependent DNA-damage responses were recently reported in melanoma cell lines ( Sauvaigo et al, 2020 Preprint ). However, an earlier publication saw no correlation between repair capacity and melanoma genotype ( Gaddameedhi et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

UVB mutagenesis differs in Nras- and Braf-mutant mouse models of melanoma

et al. 2021

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BRAF-mutant melanomas are more likely than NRAS-mutant melanomas to arise in anatomical locations protected from chronic sun damage. We hypothesized that this discrepancy in tumor location is a consequence of the differential sensitivity of BRAF and NRAS-mutant melanocytes to ultraviolet light (UV)-mediated carcinogenesis. We tested this hypothesis by comparing the mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340–400 nm) or ultraviolet-B (UVB; 280–390 nm) exposure in mouse models heterozygous for mutant Braf or homozygous for mutant Nras. Tumor onset was accelerated by UVB, but not UVA, and the resulting melanomas contained recurrent mutations affecting the RING domain of MAP3K1 and Actin-binding domain of Filamin A. Melanomas from UVB-irradiated, Braf-mutant mice averaged twice as many single-nucleotide variants and five times as many dipyrimidine variants than tumors from similarly irradiated Nras-mutant mice. A mutational signature discovered in UVB-accelerated tumors mirrored COSMIC signatures associated with human skin cancer and was more prominent in Braf- than Nras-mutant murine melanomas. These data show that a single UVB exposure yields a greater burden of mutations in murine tumors driven by oncogenic Braf.

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“…Analysis of published data revealed that A375 cells displaying low NAD(P)H: quinone oxidoreductase (NQO1) expression levels are sensitive to prooxidant agent (2,6-dichlorophenolindophenol) in contrast to G361 cells with high expression of NQO1 [ 36 ]. According to Sauviago et al [ 37 ], who studied DNA repair signatures of the different melanoma cell lines, A375 is characterized by low DNA repair capacities in contrast to SK-MEL-28 cell line that has high DNA repair capacities.…”

Section: Resultsmentioning

confidence: 99%

Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells

Pitucha

Korga-Plewko

Czylkowska

et al. 2021

IJMS

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A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.

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DNA repair-based classification of melanoma cell lines reveals an effect of mutations in BRAF and NRAS driver genes on DNA repair capacity

Cited by 3 publications

References 41 publications

UVB mutagenesis differs in NRAS- and BRAF-mutant mouse models of melanoma

UVB mutagenesis differs in NRAS- and BRAF-mutant mouse models of melanoma

UVB mutagenesis differs in Nras- and Braf-mutant mouse models of melanoma

Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells

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