High-risk Melanoma Susceptibility Genes and Pancreatic Cancer, Neural System Tumors, and Uveal Melanoma across GenoMEL

Goldstein, Alisa M., Chan, May, Harland, Mark, Gillanders, Elizabeth M., Hayward, Nicholas K., Avril, Marie-Francoise, Azizi, Esther, Bianchi-Scarra, Giovanna, Bishop, D. Timothy, Bressac-de Paillerets, Brigitte, Bruno, William, Calista, Donato, Cannon Albright, Lisa A., Demenais, Florence, Elder, David E., Ghiorzo, Paola, Gruis, Nelleke A., Hansson, Johan, Hogg, David, Holland, Elizabeth A., Kanetsky, Peter A., Kefford, Richard F., Landi, Maria Teresa, Lang, Julie, Leachman, Sancy A., MacKie, Rona M., Magnusson, Veronica, Mann, Graham J., Niendorf, Kristin, Newton Bishop, Julia, Palmer, Jane M., Puig, Susana, Puig-Butille, Joan A., de Snoo, Femke A., Stark, Mitchell, Tsao, Hensin, Tucker, Margaret A., Whitaker, Linda, Yakobson, Emanuel, The Lund Melanoma Study Group and Melanoma Genetics Consortium (GenoMEL) (2006) High-risk Melanoma Susceptibility Genes and Pancreatic Cancer, Neural System Tumors, and Uveal Melanoma across GenoMEL. Cancer research, 66 20: 9818-9828. doi:10.1158/0008-5472.CAN-06-0494


Author Goldstein, Alisa M.
Chan, May
Harland, Mark
Gillanders, Elizabeth M.
Hayward, Nicholas K.
Avril, Marie-Francoise
Azizi, Esther
Bianchi-Scarra, Giovanna
Bishop, D. Timothy
Bressac-de Paillerets, Brigitte
Bruno, William
Calista, Donato
Cannon Albright, Lisa A.
Demenais, Florence
Elder, David E.
Ghiorzo, Paola
Gruis, Nelleke A.
Hansson, Johan
Hogg, David
Holland, Elizabeth A.
Kanetsky, Peter A.
Kefford, Richard F.
Landi, Maria Teresa
Lang, Julie
Leachman, Sancy A.
MacKie, Rona M.
Magnusson, Veronica
Mann, Graham J.
Niendorf, Kristin
Newton Bishop, Julia
Palmer, Jane M.
Puig, Susana
Puig-Butille, Joan A.
de Snoo, Femke A.
Stark, Mitchell
Tsao, Hensin
Tucker, Margaret A.
Whitaker, Linda
Yakobson, Emanuel
The Lund Melanoma Study Group
Melanoma Genetics Consortium (GenoMEL)
Title High-risk Melanoma Susceptibility Genes and Pancreatic Cancer, Neural System Tumors, and Uveal Melanoma across GenoMEL
Journal name Cancer research   Check publisher's open access policy
ISSN 0008-5472
Publication date 2006-10-15
Year available 2006
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-06-0494
Open Access Status
Volume 66
Issue 20
Start page 9818
End page 9828
Total pages 11
Place of publication Philadelphia, PA, U.S.A.
Publisher American Association for Cancer Research
Language eng
Subject 111201 Cancer Cell Biology
111203 Cancer Genetics
Abstract GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, cdVS2-105A > G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available.
Formatted abstract
GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, c.IVS2-105A>G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available.
Keyword Oncology
Oncology
ONCOLOGY
Q-Index Code C1
Grant ID 1 R01 CA83115-01A2
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
School of Medicine Publications
 
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Created: Tue, 24 Mar 2009, 21:22:59 EST by Ms Lynette Adams on behalf of Medicine - Royal Brisbane and Women's Hospital