scholarly journals Familial melanoma risk genes in Queensland

2016 ◽  
Author(s):  
Jazlyn READ
Keyword(s):  
Melanoma Risk ◽  
Risk Genes ◽  
Familial Melanoma

scholarly journals Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family

2021 ◽  
Author(s):  
Kevin M. Brown ◽  
Mai Xu ◽  
Michael Sargen ◽  
Hyunbum Jang ◽  
Mingzhen Zhang ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Binding Pocket ◽  
Pi3k Pathway ◽  
Melanoma Risk ◽  
Mediterranean Populations ◽  
Risk Genes ◽  
1000 Genomes ◽  
Gtp Binding ◽  
The Us

AbstractWhile several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations, we identified a novel NRAS variant (c.170A>C, p.D57A) in a melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11 273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS. Differently from other RAS activating alterations, NRAS D57A expression is unable to activate MAPK-pathway both constitutively and after stimulation but enhances EGF-induced PI3K-pathway signaling in serum starved conditions in vitro. Consistent with in vitro data demonstrating that NRAS D57A does not enrich GTP binding, molecular modeling suggests that the D57A substitution would be expected to impair Mg2+ binding and decrease nucleotide-binding and GTPase activity of NRAS. While we cannot firmly establish NRAS c.170A>C (p.D57A) as a melanoma susceptibility variant, further investigation of NRAS as a familial melanoma gene is warranted.

From sporadic atypical nevi to familial melanoma: Risk analysis for melanoma in sporadic atypical nevus patients

2007 ◽  
Vol 56 (5) ◽  
pp. 748-752 ◽  
Author(s):  
Femke A. de Snoo ◽  
Marije W. Kroon ◽  
Wilma Bergman ◽  
Jeanet A.C. ter Huurne ◽  
Jeanine J. Houwing-Duistermaat ◽  
...  
Keyword(s):  
Risk Analysis ◽  
Melanoma Risk ◽  
Familial Melanoma ◽  
Atypical Nevi

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

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 404
Author(s):  
Lenka Stolarova ◽  
Sandra Jelinkova ◽  
Radka Storchova ◽  
Eva Machackova ◽  
Petra Zemankova ◽  
...  
Keyword(s):  
Age At Onset ◽  
Primary Melanoma ◽  
Germline Mutations ◽  
Cancer Syndrome ◽  
Melanoma Risk ◽  
Cancer History ◽  
Primary Tumors ◽  
Risk Genes ◽  
Increased Risk ◽  
Melanoma Patients

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.

scholarly journals Association between a 46-SNP Polygenic Risk Score and melanoma risk in Dutch patients with familial melanoma

2020 ◽  
pp. jmedgenet-2020-107251
Author(s):  
Thomas P Potjer ◽  
Tara W J van der Grinten ◽  
Inge M M Lakeman ◽  
Sander H Bollen ◽  
Mar Rodríguez-Girondo ◽  
...  
Keyword(s):  
Risk Score ◽  
Susceptibility Gene ◽  
Case Series ◽  
Diagnostic Value ◽  
Polygenic Risk Score ◽  
Melanoma Risk ◽  
Polygenic Risk ◽  
Familial Melanoma ◽  
Increased Risk ◽  
Familial Clustering

BackgroundFamilial clustering of melanoma suggests a shared genetic predisposition among family members, but only 10%–40% of familial cases carry a pathogenic variant in a known high-risk melanoma susceptibility gene. We investigated whether a melanoma-specific Polygenic Risk Score (PRS) is associated with melanoma risk in patients with genetically unexplained familial melanoma.MethodsDutch familial melanoma cases (n=418) were genotyped for 46 SNPs previously identified as independently associated with melanoma risk. The 46-SNP PRS was calculated and standardised to 3423 healthy controls (sPRS) and the association between PRS and melanoma risk was modelled using logistic regression. Within the case series, possible differences were further explored by investigating the PRS in relation to (1) the number of primary melanomas in a patient and (2) the extent of familial clustering of melanoma.ResultsThe PRS was significantly associated with melanoma risk, with a per-SD OR of 2.12 (95% CI 1.90 to 2.35, p<0.001), corresponding to a 5.70-fold increased risk (95% CI 3.93 to 8.28) when comparing the top 90th to the middle 40–60th PRS percentiles. The mean PRS was significantly higher in cases with multiple primary melanomas than in cases with a single melanoma (sPRS 1.17 vs 0.71, p=0.001). Conversely, cases from high-density melanoma families had a lower (but non-significant) mean PRS than cases from low-density families (sPRS 0.60 vs 0.94, p=0.204).ConclusionOur work underlines the significance of a PRS in determining melanoma susceptibility and encourages further exploration of the diagnostic value of a PRS in genetically unexplained melanoma families.

scholarly journals Dysplastic nevi as a melanoma risk factor in patients with familial melanoma

Cancer ◽  
1994 ◽  
Vol 74 (12) ◽  
pp. 3118-3125 ◽  
Author(s):  
William P. Carey ◽  
C. Jean Thompson ◽  
Marie Synnestvedt ◽  
Dupont Guerry ◽  
Allan Halpern ◽  
...  
Keyword(s):  
Risk Factor ◽  
Melanoma Risk ◽  
Familial Melanoma ◽  
Dysplastic Nevi

Familial melanoma in Spain: Preliminary report of the FAM-GEM-1 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Manuel Martin-Gonzalez ◽  
Pablo Cerezuela ◽  
Alfonso Martin-Carnicero ◽  
Teresa Puertolas ◽  
Salvador Martin-Algarra ◽  
...  
Keyword(s):  
Family History ◽  
Preliminary Report ◽  
Intermediate Risk ◽  
Registry Study ◽  
High Susceptibility ◽  
Melanoma Risk ◽  
Familial Melanoma ◽  
Molecular Features ◽  
History Of ◽  
Melanoma Patients

e20015 Background: In addition to environmental factors and phenotype, melanoma risk is determined by familial background. It is estimated that 5-10% of melanoma cases occur in a familial setting. High susceptibility genes like CDKN2A and intermediate risk like M1CR are the most known, but explain less than 1/3 of the cases, most of them cases with 2 or more first degree relatives involved, the classical definition for familial melanoma (FM). In Spain there are several local studies about epidemiology and characteristics of FM, but there are no studies that cover all the territory. Methods: FAM-GEM-1 is a national, observational, 2 years-registry study (2011-2013), conducted by the Spanish Multidisciplinary Melanoma Group (GEM), whose principal objective is to assess the rate of melanoma patients with family history of melanoma in Spain. Secondary objectives are to analyze whether patients with family history are different from sporadic melanoma in terms of clinical, pathological and molecular features; and to constitute a registry of FM in order to deeper characterise these patients in further studies. We present the exploratory results of the first 219 patients registered Results: See Table. Conclusions: We have found that almost 9% of patients have family history of melanoma. Of them, almost 3/4 fulfils familial melanoma criteria. It seems that there are not relevant differences among sporadic and familial melanoma in our registry, except for sex, although the preliminary nature of the results makes necessary more patients in order to determine if there are clinical and/or pathological differences between both groups. [Table: see text]

scholarly journals Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree

2013 ◽  
Vol 69 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Jason E. Hawkes ◽  
Pamela B. Cassidy ◽  
Prashiela Manga ◽  
Raymond E. Boissy ◽  
David Goldgar ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Melanoma Risk ◽  
Familial Melanoma ◽  
Oca2 Gene
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