Germline melanoma susceptibility and prognostic genes: A review of the literature

Ward, Katherine; Lazovich, DeAnn; Hordinsky, Maria

doi:10.1016/j.jaad.2012.02.042

Cited by 51 publications

(37 citation statements)

References 130 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent GWAS meta-analysis highlighted more than 20 genome-wide significant (GWS) (i.e., P < 5 Â 10 e8 ) risk loci, including five novel regions (Law et al, 2015). These findings corroborate the association of CM with pigmentation-associated (MC1R, TYR, SLC45A2) and neviassociated genes (MTAP, PLA2G6), as well as with loci potentially implicated in apoptosis (CASP8), DNA repair (PARP-1, ATM), metabolism (FTO), and telomerase maintenance (TERT/CLPTM1L) (Barrett et al, 2011;Iles et al, 2013;Ward et al, 2012).…”

Section: Introductionsupporting

confidence: 68%

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

Kypreou

Stefanaki

Antonopoulou

et al. 2016

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Many single nucleotide polymorphisms (SNPs) have been described as putative risk factors for melanoma. The aim of our study was to validate the most prominent genetic risk loci in an independent Greek melanoma case-control dataset and to assess their cumulative effect solely or combined with established phenotypic risk factors on individualized risk prediction. We genotyped 59 SNPs in 800 patients and 800 controls and tested their association with melanoma using logistic regression analyses. We constructed a weighted genetic risk score (GRSGWS) based on SNPs that showed genome-wide significant (GWS) association with melanoma in previous studies and assessed their impact on risk prediction. Fifteen independent SNPs from 12 loci were significantly associated with melanoma (P < 0.05). Risk score analysis yielded an odds ratio of 1.36 per standard deviation increase of the GRSGWS (P = 1.1 × 10(-7)). Individuals in the highest 20% of the GRSGWS had a 1.88-fold increase in melanoma risk compared with those in the middle quintile. By adding the GRSGWS to a phenotypic risk model, the C-statistic increased from 0.764 to 0.775 (P = 0.007). In summary, the GRSGWS is associated with melanoma risk and achieves a modest improvement in risk prediction when added to a phenotypic risk model.

show abstract

Section: Introductionsupporting

confidence: 68%

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

Kypreou

Stefanaki

Antonopoulou

et al. 2016

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…16,17 p16 Ink4a is a cyclin-dependent kinase inhibitor that blocks formation of the catalytically active CDK4/6-cyclin D complex, thereby preventing the phosphorylation of the retinoblastoma (Rb) gene and passage through the cell cycle's G1/S checkpoint (Figure 2a). [17][18][19][20] As a tumor suppressor, p16 is found in low levels in normal proliferating cells but events such as DNA damage, oncogenic stress, and aging trigger its Figure 1 Four scenarios from the proposed diagnostic algorithm for the assessment of the malignant potential of atypical spitzoid tumors. In addition to classical morphological evaluation, this algorithm applies a set of immunohistochemical assays (a dual-color of Ki67/ MART-1 (Leica Biosystems), p16 Ink4a (Roche Life Sciences), and HMB45 (Leica Biosystems)), a fluorescence in situ hybridization (FISH) with five probes (6p25, 8q24, 11q13, centromere 9, and 9p21; NeoSITE melanoma, Neogenomics Laboratories), and an array-based comparative genomic hybridization (aCGH) assay (University of California, San Francisco).…”

Section: Immunohistochemical Testsmentioning

confidence: 99%

A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment

Cho‐Vega

2016

Modern Pathology

View full text Add to dashboard Cite

Atypical spitzoid tumors are a morphologically diverse group of rare melanocytic lesions most frequently seen in children and young adults. As atypical spitzoid tumors bear striking resemblance to Spitz nevus and spitzoid melanomas clinically and histopathologically, it is crucial to determine its malignant potential and predict its clinical behavior. To date, many researchers have attempted to differentiate atypical spitzoid tumors from unequivocal melanomas based on morphological, immonohistochemical, and molecular diagnostic differences. A diagnostic algorithm is proposed here to assess the malignant potential of atypical spitzoid tumors by using a combination of immunohistochemical and cytogenetic/molecular tests. Together with classical morphological evaluation, this algorithm includes a set of immunohistochemistry assays (p16 Ink4a , a dual-color Ki67/MART-1, and HMB45), fluorescence in situ hybridization (FISH) with five probes (6p25, 8q24, 11q13, CEN9, and 9p21), and an array-based comparative genomic hybridization. This review discusses details of the algorithm, the rationale of each test used in the algorithm, and utility of this algorithm in routine dermatopathology practice. This algorithmic approach will provide a comprehensive diagnostic tool that complements conventional histological criteria and will significantly contribute to improve the diagnosis and prediction of the clinical behavior of atypical spitzoid tumors.

show abstract

“…Melanocortin 1 receptor (MC1R) is considered a moderate-risk gene, and its role in melanoma susceptibility has been widely studied [17]. MC1R , located on 16q24, is one of the master regulator genes of human pigmentation and encodes the α-melanocyte-stimulating hormone receptor 1.…”

Section: Susceptibility Genesmentioning

confidence: 99%

What Is New in Melanoma Genetics and Treatment?

et al. 2016

View full text Add to dashboard Cite

New therapies for advanced melanoma have led to major advances, which, for the first time, showed improved survival for patients with this very challenging neoplasm. These new treatments are based on gene-targeted therapies or stimulation of immune responses. However, these treatments are not without challenges in terms of resistance and toxicity. Physicians should be aware of these side effects as prompt treatment may save lives. Melanoma genetics is also unravelling new genetic risk factors involving telomere genes as well as new gene pathways at the somatic level which may soon become therapeutic targets. It is also shedding new light onto the pathology of this tumour with links to neural diseases and longevity.

show abstract

Germline melanoma susceptibility and prognostic genes: A review of the literature

Cited by 51 publications

References 130 publications

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment

What Is New in Melanoma Genetics and Treatment?

Contact Info

Product

Resources

About