TY - JOUR
T1 - Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT
AU - Taylor, Nicholas J
AU - Mitra, Nandita
AU - Qian, Lu
AU - Avril, Marie-Françoise
AU - Bishop, D Timothy
AU - Paillerets, Brigitte Bressac-de
AU - Bruno, William
AU - Calista, Donato
AU - Cuellar, Francisco
AU - Cust, Anne E
AU - Demenais, Florence
AU - Elder, David E
AU - Gerdes, Anne-Marie
AU - Ghiorzo, Paola
AU - Goldstein, Alisa M
AU - Grazziotin, Thais C
AU - Gruis, Nelleke A
AU - Hansson, Johan
AU - Harland, Mark
AU - Hayward, Nicholas K
AU - Hocevar, Marko
AU - Höiom, Veronica
AU - Holland, Elizabeth A
AU - Ingvar, Christian
AU - Landi, Maria Teresa
AU - Landman, Gilles
AU - Larre-Borges, Alejandra
AU - Mann, Graham J
AU - Nagore, Eduardo
AU - Olsson, Håkan
AU - Palmer, Jane M
AU - Perić, Barbara
AU - Pjanova, Dace
AU - Pritchard, Antonia L
AU - Puig, Susana
AU - Schmid, Helen
AU - van der Stoep, Nienke
AU - Tucker, Margaret A
AU - Wadt, Karin A W
AU - Yang, Xiaohong R
AU - Newton-Bishop, Julia A
AU - Kanetsky, Peter A
N1 - © 2019 by the American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - CDKN2A
KW - GenoMEL
KW - GenoMELPREDICT
KW - familial melanoma
KW - mutation prediction
UR - http://www.scopus.com/inward/record.url?scp=85068769924&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068769924&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2019.01.079
DO - 10.1016/j.jaad.2019.01.079
M3 - Article
C2 - 30731170
SN - 0190-9622
VL - 81
SP - 386
EP - 394
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 2
ER -