TY - JOUR
T1 - Population-based prevalence of CDKN2A mutations in Utah melanoma families
AU - Eliason, Mark J.
AU - Larson, April A.
AU - Florell, Scott R.
AU - Zone, John J.
AU - Cannon-Albright, Lisa A.
AU - Samlowski, Wolfram E.
AU - Leachman, Sancy A.
N1 - Funding Information:
We gratefully acknowledge the participation of all the individuals who took part in this study. We also appreciate genetic counseling expertise rendered by Erin Dola. This work was supported by funds from the Tom C. Mathews Jr. Familial Melanoma Research Clinic, Huntsman Cancer Foundation, the Multidisciplinary Cancer Research Training Program (AAL), and the National Institute of Health grant R01 CA102422 (LCA). This investigation was supported by the Public Health Services research grant numbers M01-RR00064 and C06-RR11234 from the National Center for Research Resources. This investigation was also supported by the Public Health Services research grant number MO1-RR00064 from the National Center for Research Resources. Data collected for this publication were assisted by the Utah Cancer Registry funded by Contract # N01-PC-35141 from the NCI with additional support from the Utah Department of Health and the University of Utah. Partial support for all data sets within the UPDB was provided by the University of Utah Huntsman Cancer Institute. Mutation testing was supported by a research grant from Myriad Genetic Laboratories, Inc. and by Dr Lisa Brailey and Dr Allen Bale of Yale Diagnostic Laboratories.
PY - 2006/3
Y1 - 2006/3
N2 - Cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) is the major melanoma predisposition gene. In order to evaluate the candidacy for genetic testing of CDKN2A mutations among melanoma prone families, it is important to identify characteristics that predict a high likelihood of carrying a CDKN2A mutation. We primarily used a unique Utah genealogical resource to identify independent melanoma prone families whom we tested for mutations in CDKN2A, cyclin-dependent kinase 4, and alternate reading frame. We sampled 60 families which met the inclusion criteria of two or more affected first-degree relatives. We found four different pathogenic CDKN2A mutations in five families, mutations of uncertain significance in two families, and known polymorphisms in three families. One of the mutations of uncertain significance, 5′ untranslated region -25C>T, has not been previously described. Among our population-based set of Utah families, the prevalence of CDKN2A mutations was 8.2% (4/49); the overall prevalence when physician-referred pedigrees were also considered was between 8.3% (5/60) and 10% (6/60). Having four or more first- or second-degree relatives with melanoma, or a family member with ≤3 primary melanomas, correlated strongly with carrying a CDKN2A mutation. We observed a significantly elevated rate of pancreatic cancer in one of four families with a deleterious CDKN2A mutation.
AB - Cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) is the major melanoma predisposition gene. In order to evaluate the candidacy for genetic testing of CDKN2A mutations among melanoma prone families, it is important to identify characteristics that predict a high likelihood of carrying a CDKN2A mutation. We primarily used a unique Utah genealogical resource to identify independent melanoma prone families whom we tested for mutations in CDKN2A, cyclin-dependent kinase 4, and alternate reading frame. We sampled 60 families which met the inclusion criteria of two or more affected first-degree relatives. We found four different pathogenic CDKN2A mutations in five families, mutations of uncertain significance in two families, and known polymorphisms in three families. One of the mutations of uncertain significance, 5′ untranslated region -25C>T, has not been previously described. Among our population-based set of Utah families, the prevalence of CDKN2A mutations was 8.2% (4/49); the overall prevalence when physician-referred pedigrees were also considered was between 8.3% (5/60) and 10% (6/60). Having four or more first- or second-degree relatives with melanoma, or a family member with ≤3 primary melanomas, correlated strongly with carrying a CDKN2A mutation. We observed a significantly elevated rate of pancreatic cancer in one of four families with a deleterious CDKN2A mutation.
UR - http://www.scopus.com/inward/record.url?scp=32844470124&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32844470124&partnerID=8YFLogxK
U2 - 10.1038/sj.jid.5700094
DO - 10.1038/sj.jid.5700094
M3 - Article
C2 - 16397522
AN - SCOPUS:32844470124
SN - 0022-202X
VL - 126
SP - 660
EP - 666
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -