Journal
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Volume 81, Issue 2, Pages 386-394Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaad.2019.01.079
Keywords
CDKN2A; familial melanoma; GenoMEL; GenoMELPREDICT; mutation prediction
Categories
Funding
- Cancer Research UK Programme Award [C588/A4994, C588/A10589]
- Cancer Research UK [C8216/A6129]
- US National Institutes of Health [CA83115, CA5558, CA147832]
- Intramural Research Program of the National Institutions of Health, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics
- Cancer Council New South Wales [77/00, 06/10]
- Cancer Institute New South Wales [CINSW 05/TPG/1-01, 10/TPG/1-02, 15/CDF/1-14]
- Cancer Council Victoria [371]
- Cancer Council Queensland [371]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
- NCI [CA88363]
- Cancer Research Foundations of Radiumhemmet
- Swedish Cancer Society
- Paulsson Trust, Lund University
- European Research Council [ERC-2011-294576]
- Spanish Fondo de Investigaciones Sanitarias [PI15/00716, PI15/00956]
- Agency for Management of University and Research Grants of the Catalan government, Spain [2014_SGR_603]
- European Commission under the 6th Framework Programme [LSHC-CT-2006-018702]
- European Commission under 7th Framework Programme, Diagnoptics
- Fundacio La Marato de TV3, Catalonia, Spain [201331-30]
- Fundacion Cientifica de la Asociacion Espanola Contra el Cancer, Spain [GCB15152978SOEN]
- Centres de Recerca de Catalunya Programme/Generalitat de Catalunya
- Italian Association for Cancer Research
- Italian Ministry of Health-Ricerca Finalizzata 2016 (Genoa)
- Programme Hospitalier de Recherche Clinique [PHRC-AOM-07-195]
- Institut National du Cancer
- Comision Honoraria de Lucha Contra el Cancer, Comision Sectorial de Investigacion Cientifica, Fundacion Manuel Perez, Montevideo, Uruguay
- Dutch Cancer Society [UL 2012-5489]
- National Health and Medical Research Council [1147843]
- Consejo Nacional de Ciencia y Tecnologia, Mexico [152256/158706]
- National Health and Medical Research Council of Australia [CA88363, NHMRC 107359, 402761, 633004, 566946, 211172]
- Fundacao de Amparoa Pesquisa do Estado de Sao Paulo [2007/04313-2]
- Centros de Investigacion Biomedica en Red de Enfermedades Raras of the Instituto de Salud Carlos III, Spain
- European Development Regional Fund A way to achieve Europe''
- MRC [MR/L01629X/1] Funding Source: UKRI
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Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.
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