Ultraviolet light and melanoma

Craig, Sarah; Earnshaw, Charles H.; Virós, Amaya

doi:10.1002/path.5039

Cited by 53 publications

(46 citation statements)

References 85 publications

(129 reference statements)

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“…TP53, NF1, and NRAS are frequently mutated genes identified in malignant melanoma. 19 TP53 mutations in melanoma are correlated with sun exposure. 20,21 In addition, TOP1 amplification was reported to be associated with more advanced and poor prognostic tumors in melanoma.…”

Section: Discussionmentioning

confidence: 97%

The Molecular Pathogenesis of Trichilemmal Carcinoma

Lee

et al. 2020

Preprint

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Section: Discussionmentioning

confidence: 97%

The Molecular Pathogenesis of Trichilemmal Carcinoma

Lee

et al. 2020

Preprint

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“…TP53, NF1, and NRAS are frequently mutated genes identi ed in malignant melanoma. 19 TP53 mutations in melanoma are correlated with sun exposure. 20,21 In addition, TOP1 ampli cation was reported to be associated with more advanced and poor prognostic tumors in melanoma.…”

Section: Discussionmentioning

confidence: 97%

The Molecular Pathogenesis of Trichilemmal Carcinoma

Lee

et al. 2020

Preprint

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Background: Trichilemmal carcinoma (TC) is an extremely rare hair follicle tumor. We aimed to explore the genetic abnormalities involved in TC to gain insight into its molecular pathogenesis.Methods: Data from patients diagnosed with TC within a 12-year period were retrospectively reviewed. Genomic DNA isolated from a formalin-fixed paraffin-embedded (FFPE) tumor tissue block was sequenced and explored for a panel of cancer genes.Results: DNA was extracted from the FFPE tissue of four patients (50% female; mean age, 51.5 years) diagnosed with TC for analysis. The tumor was located in the head and neck of three patients and in the shoulder of one patient. TP53 mutations (p.Arg213*, p.Arg249Trp, and p.Arg248Gln) were found in three patients. Fusions previously identified in melanoma were detected in two patients (TACC3-FGFR3 and ROS1-GOPC fusions). Other mutations found included NF1-truncating mutation (Arg1362*), NRAS mutation (p.Gln61Lys), TOP1 amplification, and PTEN deletion. Overall, genetic changes found in TC resemble that of other skin cancers, suggesting similar pathogenesis. All patients with TP53 mutations had aggressive clinical course, two who died (OS 93 and 36 months), and one who experienced recurrent relapse.Conclusions: We reported the genomic variations found in TC, which may give insight into the molecular pathogenesis. Overall, genetic changes found in TC resembled that of other skin cancers, suggesting similar pathogenesis. TP53 mutations was were identified in patients who had an aggressive clinical course. Genetic alterations identified may further suggest the potential treatment options of TC.

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“…Disturbances in this pathway, including oncogenic ones, may occur at different levels as a result of gene mutations -the RAS gene is one of the most frequently mutated oncogenes in human cancers [4]. Disturbances in the whole RAS/ /MAPK pathway occur in 98% of melanomas [5]. About 50% of these cancers (but for comparison, only 7-10% of all cancers in general) have a mutation in the BRAF gene.…”

Section: Introductionmentioning

confidence: 99%

“…There are also other mutations in melanoma, e.g. in tumor suppressor genes TP53, PTEN and CDKN2A, as well as in the telomerase gene promoter [5]. Also important for melanoma development are mutations induced by UV radiation, which are characterized by transitions of C->T nucleotides at the 3' end of pyrimidine dimers [8], such mutations occur in the above mentioned cancer suppressor genes, the telomerase gene and in p16.…”

Section: Introductionmentioning

confidence: 99%

“…Also important for melanoma development are mutations induced by UV radiation, which are characterized by transitions of C->T nucleotides at the 3' end of pyrimidine dimers [8], such mutations occur in the above mentioned cancer suppressor genes, the telomerase gene and in p16. However, the issue of mutations induced by UV is complicated, they are different in different melanomas and molecular classification is based more on mutations that are not caused by UV rays [5]. Moreover, it is not easy to determine whether a given mutation was caused by UV, and it is not always certain [9].…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of melanoma resistance to treatment with BRAF and MEK inhibitors

Bartnik

Fiedorowicz

Czarnecka

2019

Nowotwory. Journal of Oncology

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Several mechanisms of resistance to inhibition of BRAF activity in melanoma cells have been described so far. Genetic studies have shown that mutations in MEK1 kinase (MAP kinase kinase), which result in constitutive activation of ERK kinase, result in resistance to treatment. Another mechanism of the acquired BRAF inhibition resistance is the accumulation of activating mutations in the NRAS oncogene, which drives the activation of CRAF. This in turn leads to a permanent activation of the signal transduction to MEK and ERK. Another important mechanism of resistance is the formation of variants of the BRAF V600E gene splicing, including variants that lack exons 4 to 8 containing the RAS-binding domain. The presence of the p61 BRAF V600E variant leads to the constitutive ERK signal, which is resistant to RAF inhibition. In addition, treatment resistance is affected by hyperactivation of tyrosine kinase receptors such as platelet-derived factor receptor β (PDFRβ), insulin-like growth factor 1 receptor (IGF-1R) and erythropoietin-producing hepatocellular receptors (EPH)-leading to the induction of the 3-phosphoinositol kinase pathway (PI3K) in patients treated with BRAF or MEK inhibitors. Another interesting path of BRAFi/MEKi resistance is over-expression of the epidermal growth factor receptor (EGFR) through negative feedback in patients treated with BRAF inhibitors (BRAFi)-EGFR is not normally expressed in untreated melanomas.

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Ultraviolet light and melanoma

Cited by 53 publications

References 85 publications

The Molecular Pathogenesis of Trichilemmal Carcinoma

The Molecular Pathogenesis of Trichilemmal Carcinoma

The Molecular Pathogenesis of Trichilemmal Carcinoma

Mechanisms of melanoma resistance to treatment with BRAF and MEK inhibitors

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