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Association of germline variants in telomere maintenance genes ( and ) with spitzoid morphology in familial melanoma: A multi-center case series. | LitMetric
Background : Spitzoid morphology in familial melanoma has been associated with germline variants in , a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation.Objective : To assess if familial melanoma cases associated with germline variants in TMG (, , , and ) commonly exhibit spitzoid morphology.Methods : In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in ≥25% of tumor cells. Logistic regression was used to calculate odds ratios (OR) of spitzoid morphology compared to familial melanomas from unmatched noncarriers that were previously reviewed by a National Cancer Institute dermatopathologist.Results : Spitzoid morphology was observed in 77% (23 of 30), 75% (3 of 4), 50% (2 of 4), and 50% (1 of 2) of melanomas from individuals with germline variants in , , , and , respectively. Compared to noncarriers ( = 139 melanomas), carriers (OR = 225.1, 95% confidence interval: 51.7-980.5; < .001) and individuals with and variants (OR = 82.4, 95% confidence interval: 21.3-494.6; < .001) had increased odds of spitzoid morphology.Limitations : Findings may not be generalizable to nonfamilial melanoma cases.Conclusion : Spitzoid morphology in familial melanoma could suggest germline alteration of TMG.
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