Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

Millán-Esteban, David; Peña‐Chilet, María; García-Casado, Zaida; Manrique‐Silva, Esperanza; Requena, Celia; Bañuls, José; Löpez‐Guerrero, José Antonio; Rodríguez-Hernández, Aranzazu; Traves, Víctor; Dopazo, Joaquı́n; Virós, Amaya; Kumar, Rajiv; Nagore, Eduardo

doi:10.3390/cancers13205219

Cited by 6 publications

(7 citation statements)

References 61 publications

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“…It could be hypothesized that this fact results from the higher degree of exposure to UV radiation of the hand compared to the feet, which are usually covered by footwear. However, even the mutational prevalence of BRAFwhich was significantly higher in SM of the hand (19.4%)was lower than that reported for non-acral cumulative solar damage melanomas (37.8%) [10]. Moreover, sunburns are hardly found on the nail plate based on our clinical experience.…”

Section: Discussioncontrasting

confidence: 63%

“…Genetic alterations are known to drive melanoma development. Mutations such as those found in the coding regions of BRAF , NRAS , or NF1 , and in the promoter region of TERT ( TERT p) are the most prominently found [10], while other mutations, e.g., in KIT or GNAQ/11 in acral/mucosal or uveal melanoma, respectively, are less frequent [11]. Melanoma classification based on molecular subtypes has led to the development of targeted therapies, highlighting the value of molecular biology testing [12].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status

Millan-Esteban,

García-Casado,

Macià

et al. 2023

Dermatology

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Background: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. Objectives: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. Methods: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or Next-Generation Sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. Results: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma, but higher in SM located on the hand than on the foot. Conclusions: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.

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Section: Discussioncontrasting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status

Millan-Esteban,

García-Casado,

Macià

et al. 2023

Dermatology

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“…It would be interesting to analyze if UV irradiation is related to the effect of rs1042602 on melanoma progression. Melanomas are classified into two groups with respect to their development pathway as either nevogenic or associated with cumulative solar damage [51]. Unfortunately, we do not have data about the amount of solar damage in our patients or about high-depth sequencing data that could show a UV radiation mutation signature.…”

Section: Discussionmentioning

confidence: 99%

Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis

Sevilla

Sanchez-Diez

Cobo

et al. 2022

Life

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Cutaneous melanoma is the most aggressive of skin tumors. In order to discover new biomarkers that could help us improve prognostic prediction in melanoma patients, we have searched for germline DNA variants associated with melanoma progression. Thus, after exome sequencing of a set of melanoma patients and healthy control individuals, we identified rs1042602, an SNP within TYR, as a good candidate. After genotyping rs1042602 in 1025 patients and 773 healthy donors, we found that the rs1042602-A allele was significantly associated with susceptibility to melanoma (CATT test: p = 0.0035). Interestingly, we also observed significant differences between patients with good and bad prognosis (5 years of follow-up) (n = 664) (CATT test for all samples p = 0.0384 and for men alone p = 0.0054). Disease-free-survival (DFS) analyses also showed that patients with the A allele had shorter DFS periods. In men, the association remained significant even in a multivariate Cox Proportional-hazards model, which was adjusted for age at diagnosis, Breslow thickness, ulceration and melanoma subtype (HR 0.4; 95% confidence interval (CI) 0.20–0.83; p = 0.0139). Based on our results, we propose that rs1042602-A is a risk allele for melanoma, which also seems to be responsible for a poorer prognosis of the disease, particularly in men.

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“…Because of the restrictive method including numerous medications, a novel technique for treating melanoma is desperately required ( Bowman et al, 2021 ; Millán-Esteban et al, 2021 ; Teixido et al, 2021 ).…”

Section: Dilemma Of Skin Cancer Theranosticsmentioning

confidence: 99%

Functionalization of Nanomaterials for Skin Cancer Theranostics

Zhang

Zhu

Hou

et al. 2022

Front. Bioeng. Biotechnol.

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Skin cancer has drawn attention for the increasing incident rates and high morbidity worldwide. Timely diagnosis and efficient treatment are of paramount importance for prompt and effective therapy. Thus, the development of novel skin cancer diagnosis and treatment strategies is of great significance for both fundamental research and clinical practice. Recently, the emerging field of nanotechnology has profoundly impact on early diagnosis and better treatment planning of skin cancer. In this review, we will discuss the current encouraging advances in functional nanomaterials for skin cancer theranostics. Challenges in the field and safety concerns of nanomaterials will also be discussed.

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Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

Cited by 6 publications

References 61 publications

Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status

Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status

Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis

Functionalization of Nanomaterials for Skin Cancer Theranostics

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