Epidemiology and Risk Factors of Melanoma

Carr, Stephanie; Smith, Christina H.; Wernberg, Jessica A.

doi:10.1016/j.suc.2019.09.005

Cited by 230 publications

(217 citation statements)

References 44 publications

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“…This association has been most obvious for non-melanoma skin cancers (basal and squamous cell carcinomas) (Greinert 2009;Leiter et al 2014). For melanoma risk, an involvement of sunlight is also apparent in many cases (Carr et al 2020). The cells of origin for these tumors are thought to be epidermal keratinocytes for non-melanoma skin tumors and melanocytes or their precursors for melanoma.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of UV-induced mutations and skin cancer

Pfeifer

2020

GENOME INSTAB. DIS.

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Ultraviolet (UV) irradiation causes various types of DNA damage, which leads to specific mutations and the emergence of skin cancer in humans, often decades after initial exposure. Different UV wavelengths cause the formation of prominent UV-induced DNA lesions. Most of these lesions are removed by the nucleotide excision repair pathway, which is defective in rare genetic skin disorders referred to as xeroderma pigmentosum. A major role in inducing sunlight-dependent skin cancer mutations is assigned to the cyclobutane pyrimidine dimers (CPDs). In this review, we discuss the mechanisms of UV damage induction, the genomic distribution of this damage, relevant DNA repair mechanisms, the proposed mechanisms of how UV-induced CPDs bring about DNA replication-dependent mutagenicity in mammalian cells, and the strong signature of UV damage and mutagenesis found in skin cancer genomes.Keywords Ultraviolet · UV · Cyclobutane pyrimidine dimer · (6-4) Photoproduct · Mutations · DNA repair · Skin cancer · Melanoma Abbreviations UV light Ultraviolet light CPD Cyclobutane pyrimidine dimer (6-4)PP Pyrimidine (6-4) pyrimidone photoproduct 8-oxo-dG 8-Oxo-7,8-dihydro-2′-deoxyguanosine XP Xeroderma pigmentosum NER Nucleotide excision repair 5mC 5-Methylcytosine

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Section: Introductionmentioning

confidence: 99%

Mechanisms of UV-induced mutations and skin cancer

Pfeifer

2020

GENOME INSTAB. DIS.

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“…P16INK4a, through the inhibition of CDK4 and CDK6 (cyclin-dependent kinases 4 and 6), activates the retinoblastoma protein (RB), which blocks cellular cycle progression from phase G1 to phase S ( 12 ). CDKN2A mutations are commonly found in familial melanoma ( 13 ), and it has been hypothesized that alterations in cell cycle control genes are necessary for the acquisition of invasive potential and the transformation into invasive melanoma ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of P16INK4a in Uveal Melanoma: New Perspectives

et al. 2020

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Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite sharing the name and similar morphological features with cutaneous melanoma (CM), it is an entirely different neoplasia with a particular genetic background and clinical behavior. CDKN2A is a gene located at chromosome 9p21, encoding for P16INK4a and P14(ARF) proteins, whose role as a tumor suppressor has been clearly defined in many malignant tumors. CDKN2A frequently presents germline mutations in familial CM and epigenetic downregulation in a considerable percentage of sporadic CM. It has been hypothesized that CDKN2A alterations are early events in CM development, playing a central role in the malignant transformation of melanocytes. Alterations of the CDKN2A gene reduce the expression of P16INK4a in most CM subtypes. Immunohistochemical evaluation of P16INK4a is currently used, in association with Ki67 and HMB45, in pathology practice to discriminate between dysplastic nevi and melanoma. On the other hand, CKDN2A is rarely mutated in UM, and the immunohistochemical expression of P16INK4a has only been reported in small case series. We tested P16INK4a expression on paraffin-embedded tissue sections from 9 tissue microarrays (TMAs), built with 2 mm cores derived from 133 uveal melanoma FFPE blocks, collected from 1990 to 2018, and from selected paraffin-blocks of 3 UM liver metastases. The immunohistochemical expression of P16INK4a was assessed with a visual evaluation by light microscopy and then with a digital approach. Both approaches, with an acceptable concordance rate, revealed P16INK4a expression in a large proportion of UM cases and all liver metastases, opening new possibilities of using it in the differential diagnosis between cutaneous and uveal melanoma metastases in cases of unknown primary tumor or patients with two different primary melanomas.

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“…Along with lifestyle, genetic risk factors are significant conditions contributing to melanoma development [1,2].…”

Section: Introductionmentioning

confidence: 99%

Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients

et al. 2020

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Background: The p.E318K variant of the Melanocyte Inducing Transcription Factor (MITF) has been implicated in genetic predisposition to melanoma as an intermediate penetrance allele. However, the impact of this variant on clinico-phenotypic, as well as on dermoscopic patterns features of affected patients is not entirely defined. The purpose of our study was to assess the association between the p.E318K germline variant and clinic-phenotypical features of MITF+ compared to non-carriers (MITF−), including dermoscopic findings of melanomas and dysplastic nevi. Methods: we retrospectively analyzed a consecutive series of 1386 patients recruited between 2000 and 2017 who underwent genetic testing for CDKN2A, CDK4, MC1R and MITF germline variants in our laboratory for diagnostic/ research purposes. The patients were probands of melanoma-prone families and apparently sporadic single or multiple primary melanoma patients. For all, we collected clinical, pathological information and dermoscopic images of the histopathologically diagnosed melanomas and dysplastic nevi, when available. Results: After excluding patients positive for CDKN2A/CDK4 pathogenic variants and those affected by non-cutaneous melanomas, our study cohort comprised 984 cutaneous melanoma patients, 22 MITF+ and 962 MITF−. MITF+ were more likely to develop dysplastic nevi and multiple primary melanomas. Nodular melanoma was more common in MITF+ patients (32% compared to 19% in MITF−). MITF+ patients showed more frequently dysplastic nevi and melanomas with uncommon dermoscopic patterns (unspecific), as opposed to MITF− patients, whose most prevalent pattern was the multicomponent. Conclusions: MITF+ patients tend to develop melanomas and dysplastic nevi with histopathological features, frequency and dermoscopic patterns often different from those prevalent in MITF− patients. Our results emphasize the importance of melanoma prevention programs for MITF+ patients, including dermatologic surveillance with digital follow-up.

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Epidemiology and Risk Factors of Melanoma

Cited by 230 publications

References 44 publications

Mechanisms of UV-induced mutations and skin cancer

Mechanisms of UV-induced mutations and skin cancer

Expression of P16INK4a in Uveal Melanoma: New Perspectives

Clinical, pathological and dermoscopic phenotype of MITF p.E318K carrier cutaneous melanoma patients

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