Hereditary melanoma: Update on syndromes and management

Soura, Efthymia; Eliades, Philip; Shannon, Kristen M.; Stratigos, Alexander J.; Tsao, Hensin

doi:10.1016/j.jaad.2015.08.037

Cited by 60 publications

(21 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CZMELAC panel (CZech MELAnoma panel for Cancer predisposition) targeted 217 genes including (i) high-to-moderate and (ii) low melanoma risk genes, (iii) hereditary cancer syndrome genes with an uncertain melanoma risk, (iv) genes associated with “melanoma” in the Phenopedia database with at least two entries (assessed June 16, 2016; Table 2 ) [ 6 , 9 , 14 , 16 , 22 , 23 , 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

et al. 2020

View full text Add to dashboard Cite

Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of germline variants, we analyzed 264 Czech melanoma patients indicated for testing due to early melanoma (at <25 years) or the presence of multiple primary melanoma/melanoma and other cancer in their personal and/or family history. All patients were analyzed by panel next-generation sequencing targeting 217 genes in four groups: high-to-moderate melanoma risk genes, low melanoma risk genes, cancer syndrome genes, and other genes with an uncertain melanoma risk. Population frequencies were assessed in 1479 population-matched controls. Selected POT1 and CHEK2 variants were characterized by functional assays. Mutations in clinically relevant genes were significantly more frequent in melanoma patients than in controls (31/264; 11.7% vs. 58/1479; 3.9%; p = 2.0 × 10−6). A total of 9 patients (3.4%) carried mutations in high-to-moderate melanoma risk genes (CDKN2A, POT1, ACD) and 22 (8.3%) patients in other cancer syndrome genes (NBN, BRCA1/2, CHEK2, ATM, WRN, RB1). Mutations in high-to-moderate melanoma risk genes (OR = 52.2; 95%CI 6.6–413.1; p = 3.2 × 10−7) and in other cancer syndrome genes (OR = 2.3; 95%CI 1.4–3.8; p = 0.003) were significantly associated with melanoma risk. We found an increased potential to carry these mutations (OR = 2.9; 95%CI 1.2–6.8) in patients with double primary melanoma, melanoma and other primary cancer, but not in patients with early age at onset. The analysis revealed affected genes in Czech melanoma patients and identified individuals who may benefit from genetic testing and future surveillance management of mutation carriers.

show abstract

Section: Methodsmentioning

confidence: 99%

Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The BAP1 functions as part of the DNA damage response proteins promoting repair of DNA double-strand breaks [38]. However, the exact mechanism of BAP1 mutations that promote melanoma genesis is yet to be elucidated [39].…”

Section: Human Melanomamentioning

confidence: 99%

“…Germline mutation in telomerase reverse transcriptase ( TERT gene) [40] and other proteins, which protect the ends of chromosomes from deterioration and the cells from senescence, were also reported in melanoma affected families. Mutations in the protection of telomeres 1 ( POT1 ) gene may lead to insufficient capping of telomeres by the shelterin complex and may also regulate telomerase function [39]. Loss-of-function, missense mutations or other POT1 variants were observed in familial melanoma patients in the United Kingdom, the Netherlands, and Australia [41] and in another study also in Italy, USA, and France [42].…”

Section: Human Melanomamentioning

confidence: 99%

Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma

Horák

Palanová

Čížková

et al. 2019

Genes

View full text Add to dashboard Cite

National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance.

show abstract

“…98 Germline mutations in BAP-1, known as BAP-1 tumor syndrome, confer inherited susceptibility to the aforementioned cutaneous and internal malignancies. 99 Loss of BAP-1 expression can be identified in melanocytic lesions with IHC analysis 100 and may prove most useful in evaluation of atypical spitzoid melanocytic proliferations. 101–103 BAP-1 expression is also being evaluated as a potential prognostic marker for melanoma, especially uveal melanoma.…”

Section: Diagnosismentioning

confidence: 99%

Atypical Melanocytic Proliferations: A Review of the Literature

et al. 2018

View full text Add to dashboard Cite

Because the diagnosis dictates treatment, it is incumbent to establish a diagnosis as definitive as possible, obtaining second or third opinions and using ancillary studies when appropriate. When the diagnosis remains uncertain, it is difficult to provide guidelines for treatment. Clinical care decisions for patients with an uncertain diagnosis are best done on a case-by-case basis weighing probabilities of adverse outcomes against potential benefits and risks from various treatment options.

show abstract

Hereditary melanoma: Update on syndromes and management

Cited by 60 publications

References 52 publications

Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma

Atypical Melanocytic Proliferations: A Review of the Literature

Contact Info

Product

Resources

About