Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

Publication date: Feb 04, 2019

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 melanoma families and whether performance improvements can be achieved.

2,116 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 (CI) along with net reclassification indices (NRI) as performance metrics.

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

Taylor, N.J., Mitra, N., Qian, L., Avril, M.F., Bishop, D.T., Paillerets, B.B., Bruno, W., Calista, D., Cuellar, F., Cust, A.E., Demenais, F., Elder, D.E., Gerdes, A.M., Ghiorzo, P., Goldstein, A.M., Grazziotin, T.C., Gruis, N.A., Hansson, J., Harland, M., Hayward, N.K., Hocevar, M., , H”oiom, Holland, E.A., Ingvar, C., Landi, M.T., Landman, G., Larre-Borges, A., Mann, G.J., Nagore, E., Olsson, H., Palmer, J.M., Peri’c, B., Pjanova, D., Pritchard, A.L., Puig, S., Schmid, H., van der Stoep, N., Tucker, M.A., Wadt, K.A.W., Yang, X.R., Newton-Bishop, J.A., Kanetsky, P.A., and Group, GenoMEL Study. Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT. 21640. 2019 J Am Acad Dermatol.



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