Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT
(2019) In Journal of the American Academy of Dermatology 81(2). p.386-394- Abstract
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 melanoma families and whether performance improvements can be achieved.
METHODS: 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... (More)
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 melanoma families and whether performance improvements can be achieved.
METHODS: 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.
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<0.0001) 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 dataset 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 counselling these patients towards genetic testing or cancer risk counselling.
(Less)
- author
- Taylor, Nicholas J
; Mitra, Nandita
; Qian, Lu
; Avril, Marie-Françoise
; Bishop, D Timothy
; Paillerets, Brigitte Bressac-de
; Bruno, William
; Calista, Donato
; Cuellar, Francisco
; Cust, Anne E
; Demenais, Florence
; Elder, David E
; Gerdes, Anne-Marie
; Ghiorzo, Paola
; Goldstein, Alisa M
; Grazziotin, Thais C
; Gruis, Nelleke A
; Hansson, Johan
; Harland, Mark
; Hayward, Nicholas K
; Hocevar, Marko
; Höiom, Veronica
; Holland, Elizabeth A
; Ingvar, Christian
LU
; Landi, Maria Teresa
; Landman, Gilles
; Larre-Borges, Alejandra
; Mann, Graham J
; Nagore, Eduardo
; Olsson, Håkan
LU
; Palmer, Jane M
; Perić, Barbara
; Pjanova, Dace
; Pritchard, Antonia L
; Puig, Susana
; Schmid, Helen
; van der Stoep, Nienke
; Tucker, Margaret A
; Wadt, Karin A W
; Yang, Xiaohong R
; Newton-Bishop, Julia A
and Kanetsky, Peter A
(Less) - author collaboration
- organization
- publishing date
- 2019-08
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Academy of Dermatology
- volume
- 81
- issue
- 2
- pages
- 386 - 394
- publisher
- Elsevier
- external identifiers
-
- scopus:85068769924
- pmid:30731170
- ISSN
- 0190-9622
- DOI
- 10.1016/j.jaad.2019.01.079
- language
- English
- LU publication?
- yes
- id
- 10c123b0-f236-4bff-a830-f8308a594272
- date added to LUP
- 2019-02-27 12:06:05
- date last changed
- 2025-01-09 03:14:42
@article{10c123b0-f236-4bff-a830-f8308a594272,
abstract = {{<p>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 melanoma families and whether performance improvements can be achieved.</p><p>METHODS: 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.</p><p>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<0.0001) in GenoMELPREDICT (AUC=0.772; 95%CI: 0.750, 0.793; NRI=0.40). Including phenotypic risk factors did not improve performance.</p><p>CONCLUSION: The MELPREDICT model functioned well in a global dataset 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 counselling these patients towards genetic testing or cancer risk counselling.</p>}},
author = {{Taylor, Nicholas J and Mitra, Nandita and Qian, Lu and Avril, Marie-Françoise and Bishop, D Timothy and Paillerets, Brigitte Bressac-de and Bruno, William and Calista, Donato and Cuellar, Francisco and Cust, Anne E and Demenais, Florence and Elder, David E and Gerdes, Anne-Marie and Ghiorzo, Paola and Goldstein, Alisa M and Grazziotin, Thais C and Gruis, Nelleke A and Hansson, Johan and Harland, Mark and Hayward, Nicholas K and Hocevar, Marko and Höiom, Veronica and Holland, Elizabeth A and Ingvar, Christian and Landi, Maria Teresa and Landman, Gilles and Larre-Borges, Alejandra and Mann, Graham J and Nagore, Eduardo and Olsson, Håkan and Palmer, Jane M and Perić, Barbara and Pjanova, Dace and Pritchard, Antonia L and Puig, Susana and Schmid, Helen and van der Stoep, Nienke and Tucker, Margaret A and Wadt, Karin A W and Yang, Xiaohong R and Newton-Bishop, Julia A and Kanetsky, Peter A}},
issn = {{0190-9622}},
language = {{eng}},
number = {{2}},
pages = {{386--394}},
publisher = {{Elsevier}},
series = {{Journal of the American Academy of Dermatology}},
title = {{Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT}},
url = {{http://dx.doi.org/10.1016/j.jaad.2019.01.079}},
doi = {{10.1016/j.jaad.2019.01.079}},
volume = {{81}},
year = {{2019}},
}