Molecular characterization of fast-growing melanomas

Gaudy‐Marqueste, C.; Macagno, Nicolas; Loundou, Anderson; Pellegrino, Eric; Ouafik, L’Houcine; Budden, Timothy; Mundra, Piyushkumar A.; Gremel, Gabriela; Akhras, Victoria; Lin, Liyan; Cook, Martin; Kumar, Rajiv; Grob, Jean‐Jacques; Nagore, Eduardo; Marais, Richard; Virós, Amaya

doi:10.1016/j.jaad.2021.07.011

Cited by 12 publications

(9 citation statements)

References 44 publications

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“…The UVR-mutational landscapes of CM and skin melanoma are much more similar than previously thought, with very high mutational burden and distinct driving oncogenic RAF/RAS mutations, maintaining a hyper-activated MAPK/ERK pathway [8,9,11,13,14,21,23]. Despite high mutational burden, most melanoma tumors retain wtp53 and have instead developed alternative mechanisms, most commonly overproduction of Mdm2, for disabling p53 expression and function [8,9,11,13,15,21,23]. While studies in several melanoma types demonstrated that p53 activity could thus be restored, such strategies have not been investigated in CM.…”

Section: Discussionmentioning

confidence: 92%

“…Presence of a UVR-signature as the inducer of DNA damage differentiates CM from all other mucosal melanoma [8, 9, 11, 13-15, 21, 23]. The UVR-mutational landscapes of CM and skin melanoma are much more similar than previously thought, with very high mutational burden and distinct driving oncogenic RAF/RAS mutations, maintaining a hyper-activated MAPK/ERK pathway [8,9,11,13,14,21,23]. Despite high mutational burden, most melanoma tumors retain wtp53 and have instead developed alternative mechanisms, most commonly overproduction of Mdm2, for disabling p53 expression and function [8,9,11,13,15,21,23].…”

Section: Discussionmentioning

confidence: 99%

“…They can arise in almost every structure with mucosal epithelium such as anorectum, vulva and vagina, nasal and oral cavities, or within the mucosal membrane covering the eye, the conjunctiva. Conjunctival melanoma (CM) not only is the most frequent mucosal melanoma but also distinguishes itself within this category by being the single one with UVR exposure as an etiologic factor [8,9,11,13]. Furthermore, unlike other mucosal melanomas and suggesting common UVR-etiology, the rates of CM are increasing, in parallel to skin melanoma incidence [8,[14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

Song¹,

Cismas²,

Crudden³

et al. 2021

Oncogene

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

Song¹,

Cismas²,

Crudden³

et al. 2021

Oncogene

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“…Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome [ 5 , 6 , 7 , 8 ]. Recent progresses in immunomodulatory therapy have been added to the current arsenal in the fight against melanoma, but there are considerable efforts to identify suitable biomarkers for early diagnosis, staging, differential diagnosis, prognosis, and tailored therapy [ 5 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

et al. 2022

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Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma’s clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or “inflammasome”, its association with adipose tissue products, including the release of “extracellular vesicles”, and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma’s particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

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“…CM is a significant cause of skin cancer-related death worldwide with a poor prognosis [ 3 , 27 ]. Despite advances in CM treatment with targeted therapies combined with immunotherapy in recent decades, cross-drug resistance still affects the prognosis of patients.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Ferroptosis-Related DNA Methylation Signature for Predicting the Prognosis and Guiding the Treatment in Cutaneous Melanoma

Guo

Wang

et al. 2022

IJMS

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Cutaneous melanoma (CM) is one of the most aggressive skin tumors with a poor prognosis. Ferroptosis is a newly discovered form of regulated cell death that is closely associated with cancer development and immunotherapy. The aim of this study was to establish and validate a ferroptosis-related gene (FRG) DNA methylation signature to predict the prognosis of CM patients using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. A reliable four-FRG DNA methylation prognostic signature was constructed via Cox regression analysis based on TCGA database. Kaplan–Meier analysis showed that patients in the high-risk group tended to have a shorter overall survival (OS) than the low-risk group in both training TCGA and validation GEO cohorts. Time-dependent receiver operating characteristic (ROC) analysis showed the areas under the curve (AUC) at 1, 3, and 5 years were 0.738, 0.730, and 0.770 in TCGA cohort and 0.773, 0.775, and 0.905 in the validation cohort, respectively. Univariate and multivariate Cox regression analyses indicated that the signature was an independent prognostic indicator of OS in patients with CM. Immunogenomic profiling showed the low-risk group of patients had a higher immunophenoscore, and most immune checkpoints were negatively associated with the risk signature. Functional enrichment analysis revealed that immune response and immune-related pathways were enriched in the low-risk group. In conclusion, we established and validated a four-FRG DNA methylation signature that independently predicts prognosis in CM patients. This signature was strongly correlated with the immune landscape, and may serve as a biomarker to guide clinicians in making more precise and personalized treatment decisions for CM patients.

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Molecular characterization of fast-growing melanomas

Cited by 12 publications

References 44 publications

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma

The Interplay between Tumour Microenvironment Components in Malignant Melanoma

Identification and Validation of Ferroptosis-Related DNA Methylation Signature for Predicting the Prognosis and Guiding the Treatment in Cutaneous Melanoma

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