High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL

Alisa M. Goldstein, May Chan, Mark Harland, Elizabeth M. Gillanders, Nicholas K. Hayward, Marie Francoise Avril, Esther Azizi, Giovanna Bianchi-Scarra, D. Timothy Bishop, Brigitte Bressac-De Paillerets, William Bruno, Donato Calista, Lisa A Cannon Albright, Florence Demenais, David E. Elder, Paola Ghiorzo, Nelleke A. Gruis, Johan Hansson, David Hogg, Elizabeth A. HollandPeter A. Kanetsky, Richard F. Kefford, Maria Teresa Landi, Julie Lang, Sancy Leachman, Rona M. MacKie, Veronica Magnusson, Graham J. Mann, Kristin Niendorf, Julia Newton Bishop, Jane M. Palmer, Susana Puig, Joan A. Puig-Butille, Femke A. De Snoo, Mitchell Stark, Hensin Tsao, Margaret A. Tucker, Linda Whitaker, Emanuel Yakobson, J. Malvehy, C. Badenas, R. Cervera, Francisco Cuellar, Rosa Martí, Joan Brunet-Vidal, Guang Yang, Nicholas Martin, David Whiteman, Adele Green, Joanne Aitken, Paola Minghetti, Michela Mantelli, Lorenza Pastorino, Sabina Nasti, Sara Gargiulo, Sara Gliori, Sushila Mistry, Juliette Randerson-Moor, Wilma Bergman, Jeanet A C Ter Huurne, Clasine Van Der Drift, Leny Van Mourik, Coby Out-Luiting, Frans Van Nieuwpoort, Valerie Chaudru, Agnes Chompret, Caroline Kanengiesser, J. L. Michel, F. Grange, B. Sassolas, J. M. Limacher, D. Couillet, F. Truchetet, J. P. Cesarini, F. Boitier, J. Chevrant-Breton, C. Lasset, M. Longy, P. Joly, N. Basset-Seguin, T. Lesimple, C. Dugast, Arupa Ganguly, Michael Ming, Patricia Van Belle, Anton Platz, Suzanne Egyhazi, Rainer Tuominen, Diana Linden, Helen Schmid, Alon Scope, Felix Pavlotsky, Eitan Friedman, Mark Eliason, Christian Ingvar, Ake Borg, Johan Westerdahl, Anna Masback, Hakan Olsson

Research output: Contribution to journalArticle

258 Citations (Scopus)

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.M531, 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.

Original languageEnglish (US)
Pages (from-to)9818-9828
Number of pages11
JournalCancer Research
Volume66
Issue number20
DOIs
StatePublished - Oct 15 2006
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Melanoma
Mutation
Genes
Neoplasms
Reading Frames
Uveal melanoma
Tumor Suppressor Protein p14ARF
p16 Genes
North America
Sweden
Netherlands
Spain
Italy
France

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goldstein, A. M., Chan, M., Harland, M., Gillanders, E. M., Hayward, N. K., Avril, M. F., ... Olsson, H. (2006). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Research, 66(20), 9818-9828. https://doi.org/10.1158/0008-5472.CAN-06-0494

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; Albright, Lisa A Cannon; 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; MacKie, Rona M.; Magnusson, Veronica; Mann, Graham J.; Niendorf, Kristin; Bishop, Julia Newton; Palmer, Jane M.; Puig, Susana; Puig-Butille, Joan A.; De Snoo, Femke A.; Stark, Mitchell; Tsao, Hensin; Tucker, Margaret A.; Whitaker, Linda; Yakobson, Emanuel; Malvehy, J.; Badenas, C.; Cervera, R.; Cuellar, Francisco; Martí, Rosa; Brunet-Vidal, Joan; Yang, Guang; Martin, Nicholas; Whiteman, David; Green, Adele; Aitken, Joanne; Minghetti, Paola; Mantelli, Michela; Pastorino, Lorenza; Nasti, Sabina; Gargiulo, Sara; Gliori, Sara; Mistry, Sushila; Randerson-Moor, Juliette; Bergman, Wilma; Ter Huurne, Jeanet A C; Van Der Drift, Clasine; Van Mourik, Leny; Out-Luiting, Coby; Van Nieuwpoort, Frans; Chaudru, Valerie; Chompret, Agnes; Kanengiesser, Caroline; Michel, J. L.; Grange, F.; Sassolas, B.; Limacher, J. M.; Couillet, D.; Truchetet, F.; Cesarini, J. P.; Boitier, F.; Chevrant-Breton, J.; Lasset, C.; Longy, M.; Joly, P.; Basset-Seguin, N.; Lesimple, T.; Dugast, C.; Ganguly, Arupa; Ming, Michael; Van Belle, Patricia; Platz, Anton; Egyhazi, Suzanne; Tuominen, Rainer; Linden, Diana; Schmid, Helen; Scope, Alon; Pavlotsky, Felix; Friedman, Eitan; Eliason, Mark; Ingvar, Christian; Borg, Ake; Westerdahl, Johan; Masback, Anna; Olsson, Hakan.

In: Cancer Research, Vol. 66, No. 20, 15.10.2006, p. 9818-9828.

Research output: Contribution to journalArticle

Goldstein, AM, Chan, M, Harland, M, Gillanders, EM, Hayward, NK, Avril, MF, Azizi, E, Bianchi-Scarra, G, Bishop, DT, Bressac-De Paillerets, B, Bruno, W, Calista, D, Albright, LAC, Demenais, F, Elder, DE, Ghiorzo, P, Gruis, NA, Hansson, J, Hogg, D, Holland, EA, Kanetsky, PA, Kefford, RF, Landi, MT, Lang, J, Leachman, S, MacKie, RM, Magnusson, V, Mann, GJ, Niendorf, K, Bishop, JN, Palmer, JM, Puig, S, Puig-Butille, JA, De Snoo, FA, Stark, M, Tsao, H, Tucker, MA, Whitaker, L, Yakobson, E, Malvehy, J, Badenas, C, Cervera, R, Cuellar, F, Martí, R, Brunet-Vidal, J, Yang, G, Martin, N, Whiteman, D, Green, A, Aitken, J, Minghetti, P, Mantelli, M, Pastorino, L, Nasti, S, Gargiulo, S, Gliori, S, Mistry, S, Randerson-Moor, J, Bergman, W, Ter Huurne, JAC, Van Der Drift, C, Van Mourik, L, Out-Luiting, C, Van Nieuwpoort, F, Chaudru, V, Chompret, A, Kanengiesser, C, Michel, JL, Grange, F, Sassolas, B, Limacher, JM, Couillet, D, Truchetet, F, Cesarini, JP, Boitier, F, Chevrant-Breton, J, Lasset, C, Longy, M, Joly, P, Basset-Seguin, N, Lesimple, T, Dugast, C, Ganguly, A, Ming, M, Van Belle, P, Platz, A, Egyhazi, S, Tuominen, R, Linden, D, Schmid, H, Scope, A, Pavlotsky, F, Friedman, E, Eliason, M, Ingvar, C, Borg, A, Westerdahl, J, Masback, A & Olsson, H 2006, 'High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL', Cancer Research, vol. 66, no. 20, pp. 9818-9828. https://doi.org/10.1158/0008-5472.CAN-06-0494
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 ; Albright, Lisa A Cannon ; 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 ; MacKie, Rona M. ; Magnusson, Veronica ; Mann, Graham J. ; Niendorf, Kristin ; Bishop, Julia Newton ; Palmer, Jane M. ; Puig, Susana ; Puig-Butille, Joan A. ; De Snoo, Femke A. ; Stark, Mitchell ; Tsao, Hensin ; Tucker, Margaret A. ; Whitaker, Linda ; Yakobson, Emanuel ; Malvehy, J. ; Badenas, C. ; Cervera, R. ; Cuellar, Francisco ; Martí, Rosa ; Brunet-Vidal, Joan ; Yang, Guang ; Martin, Nicholas ; Whiteman, David ; Green, Adele ; Aitken, Joanne ; Minghetti, Paola ; Mantelli, Michela ; Pastorino, Lorenza ; Nasti, Sabina ; Gargiulo, Sara ; Gliori, Sara ; Mistry, Sushila ; Randerson-Moor, Juliette ; Bergman, Wilma ; Ter Huurne, Jeanet A C ; Van Der Drift, Clasine ; Van Mourik, Leny ; Out-Luiting, Coby ; Van Nieuwpoort, Frans ; Chaudru, Valerie ; Chompret, Agnes ; Kanengiesser, Caroline ; Michel, J. L. ; Grange, F. ; Sassolas, B. ; Limacher, J. M. ; Couillet, D. ; Truchetet, F. ; Cesarini, J. P. ; Boitier, F. ; Chevrant-Breton, J. ; Lasset, C. ; Longy, M. ; Joly, P. ; Basset-Seguin, N. ; Lesimple, T. ; Dugast, C. ; Ganguly, Arupa ; Ming, Michael ; Van Belle, Patricia ; Platz, Anton ; Egyhazi, Suzanne ; Tuominen, Rainer ; Linden, Diana ; Schmid, Helen ; Scope, Alon ; Pavlotsky, Felix ; Friedman, Eitan ; Eliason, Mark ; Ingvar, Christian ; Borg, Ake ; Westerdahl, Johan ; Masback, Anna ; Olsson, Hakan. / High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. In: Cancer Research. 2006 ; Vol. 66, No. 20. pp. 9818-9828.
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title = "High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL",
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.M531, 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.",
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day = "15",
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language = "English (US)",
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TY - JOUR

T1 - High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL

AU - Goldstein, Alisa M.

AU - Chan, May

AU - Harland, Mark

AU - Gillanders, Elizabeth M.

AU - Hayward, Nicholas K.

AU - Avril, Marie Francoise

AU - Azizi, Esther

AU - Bianchi-Scarra, Giovanna

AU - Bishop, D. Timothy

AU - Bressac-De Paillerets, Brigitte

AU - Bruno, William

AU - Calista, Donato

AU - Albright, Lisa A Cannon

AU - Demenais, Florence

AU - Elder, David E.

AU - Ghiorzo, Paola

AU - Gruis, Nelleke A.

AU - Hansson, Johan

AU - Hogg, David

AU - Holland, Elizabeth A.

AU - Kanetsky, Peter A.

AU - Kefford, Richard F.

AU - Landi, Maria Teresa

AU - Lang, Julie

AU - Leachman, Sancy

AU - MacKie, Rona M.

AU - Magnusson, Veronica

AU - Mann, Graham J.

AU - Niendorf, Kristin

AU - Bishop, Julia Newton

AU - Palmer, Jane M.

AU - Puig, Susana

AU - Puig-Butille, Joan A.

AU - De Snoo, Femke A.

AU - Stark, Mitchell

AU - Tsao, Hensin

AU - Tucker, Margaret A.

AU - Whitaker, Linda

AU - Yakobson, Emanuel

AU - Malvehy, J.

AU - Badenas, C.

AU - Cervera, R.

AU - Cuellar, Francisco

AU - Martí, Rosa

AU - Brunet-Vidal, Joan

AU - Yang, Guang

AU - Martin, Nicholas

AU - Whiteman, David

AU - Green, Adele

AU - Aitken, Joanne

AU - Minghetti, Paola

AU - Mantelli, Michela

AU - Pastorino, Lorenza

AU - Nasti, Sabina

AU - Gargiulo, Sara

AU - Gliori, Sara

AU - Mistry, Sushila

AU - Randerson-Moor, Juliette

AU - Bergman, Wilma

AU - Ter Huurne, Jeanet A C

AU - Van Der Drift, Clasine

AU - Van Mourik, Leny

AU - Out-Luiting, Coby

AU - Van Nieuwpoort, Frans

AU - Chaudru, Valerie

AU - Chompret, Agnes

AU - Kanengiesser, Caroline

AU - Michel, J. L.

AU - Grange, F.

AU - Sassolas, B.

AU - Limacher, J. M.

AU - Couillet, D.

AU - Truchetet, F.

AU - Cesarini, J. P.

AU - Boitier, F.

AU - Chevrant-Breton, J.

AU - Lasset, C.

AU - Longy, M.

AU - Joly, P.

AU - Basset-Seguin, N.

AU - Lesimple, T.

AU - Dugast, C.

AU - Ganguly, Arupa

AU - Ming, Michael

AU - Van Belle, Patricia

AU - Platz, Anton

AU - Egyhazi, Suzanne

AU - Tuominen, Rainer

AU - Linden, Diana

AU - Schmid, Helen

AU - Scope, Alon

AU - Pavlotsky, Felix

AU - Friedman, Eitan

AU - Eliason, Mark

AU - Ingvar, Christian

AU - Borg, Ake

AU - Westerdahl, Johan

AU - Masback, Anna

AU - Olsson, Hakan

PY - 2006/10/15

Y1 - 2006/10/15

N2 - 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.M531, 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.

AB - 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.M531, 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=33750567811&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-06-0494

DO - 10.1158/0008-5472.CAN-06-0494

M3 - Article

C2 - 17047042

AN - SCOPUS:33750567811

VL - 66

SP - 9818

EP - 9828

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 20

ER -