TY - JOUR
T1 - Localization of a novel melanoma susceptibility locus to 1p22
AU - Gillanders, Elizabeth
AU - Juo, Sub Hang Hank
AU - Holland, Elizabeth A.
AU - Jones, Mary Pat
AU - Nancarrow, Derek
AU - Freas-Lutz, Diana
AU - Sood, Raman
AU - Park, Naeun
AU - Faruque, Mezbah
AU - Markey, Carol
AU - Kefford, Richard F.
AU - Palmer, Jane
AU - Bergman, Wilma
AU - Bishop, D. Timothy
AU - Tucker, Margaret A.
AU - Bressac-De Paillerets, Brigitte
AU - Hansson, Johan
AU - Stark, Mitchell
AU - Gruis, Nelleke
AU - Bishop, Julia Newton
AU - Goldstein, Alisa M.
AU - Bailey-Wilson, Joan E.
AU - Mann, Graham J.
AU - Hayward, Nicholas
AU - Trent, Jeffrey
N1 - Funding Information:
We are very grateful to all the family members who willingly participated in this study. The authors wish to acknowledge the contributions to this work that were made by Mary C. Fraser, M.S.N.; Laura Fontaine, B.S.N.; and Deborah Zametkin, M.S.N. We are grateful to the Sydney Melanoma Unit—in particular, to Bill McCarthy and John Thompson—and to John Kelly (Victorian Melanoma Service) for referring families, and we acknowledge the contributions of Barbara Peters, Judy Salmon, and Helen Shaw to their characterization. The work in Sydney was supported by grants from the Australian National Health and Medical Research Council, the Cancer Council NSW, the Melanoma and Skin Cancer Research Institute, and the University of Sydney. Work in Queensland was supported by National Institutes of Health grant CA88363 and by the National Health and Medical Research Council of Australia. The Department of Oncology-Pathology, Radiumhemmet, Karolinska Hospital was supported by grants from The Cancer Society of Stockholm and The King Gustav V Jubilee Fund, Stockholm. We would also like to thank Dr. Izabela Makalowska and Michal Galdzicki for their contributions in the analysis of the candidate interval through use of bioinformatics tools. The following groups from the Melanoma Genetics Consortium participated in this research: Queensland Cancer Fund Research Unit, Joint Experimental Oncology Programme of the Queensland University and Queensland Institute of Medical Research, Brisbane, Australia: Nicholas Hayward, Derek Nancarrow, Jane Palmer, Nicholas Martin, Adele Green, Joanne Aitken, David Whiteman, Marilyn Walters, and Megan Campbell; Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Sydney, Australia: Richard F. Kefford, Graham J. Mann, Helen Schmid, Elizabeth A. Holland; Department of Dermatology and Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands: Wilma Bergman, Rune Frants, Nelleke Gruis, Pieter van der Velden, and Femke de Snoo; Genetic Epidemiology Division, Cancer Research UK Clinical Centre, Leeds, United Kingdom: Jenny Barrett, Julia Newton Bishop, Timothy Bishop, and Mark Harland; Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States: Alisa M. Goldstein and Margaret A. Tucker; Institut Gustave Rousy, Villejuif, France: Marie-Françoise Avril, Brigitte Bressac de Paillerets, and Agnès Chompret; Department of Oncology-Pathology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden: Johan Hansson, Anton Platz, and Jamileh Hashemi; and Lund Cancer Center, Department of Oncology, University Hospital, Lund, Sweden: Christian Ingvar, Åke Borg, Johan Westerdahl, Anna Måsbäck, and Håkan Olsson.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Over the past 20 years, the incidence of cutaneous malignant melanoma (CMM) has increased dramatically worldwide. A positive family history of the disease is among the most established risk factors for CMM; it is estimated that 10% of CMM cases result from an inherited predisposition. Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM. Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. The highest two-point parametric LOD score (1.82; recombination fraction [θ] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (θ = 0) and a nonparametric LOD score of 4.19 were found at D1S2779 in nine families selected for early age at onset. Additional typing yielded seven adjacent markers with LOD scores >3 in this subset, with the highest parametric LOD score, 4.95 (θ = 0) (nonparametric LOD score 5.37), at D1S2776. Analysis of 33 additional multiplex families with CMM from several continents provided further evidence for linkage to the 1p22 region, again strongest in families with the earliest mean age at diagnosis. A nonparametric ordered sequential analysis was used, based on the average age at diagnosis in each family. The highest LOD score, 6.43, was obtained at D1S2779 and occurred when the 15 families with the earliest ages at onset were included. These data provide significant evidence of a novel susceptibility gene for CMM located within chromosome band 1p22.
AB - Over the past 20 years, the incidence of cutaneous malignant melanoma (CMM) has increased dramatically worldwide. A positive family history of the disease is among the most established risk factors for CMM; it is estimated that 10% of CMM cases result from an inherited predisposition. Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM. Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. The highest two-point parametric LOD score (1.82; recombination fraction [θ] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (θ = 0) and a nonparametric LOD score of 4.19 were found at D1S2779 in nine families selected for early age at onset. Additional typing yielded seven adjacent markers with LOD scores >3 in this subset, with the highest parametric LOD score, 4.95 (θ = 0) (nonparametric LOD score 5.37), at D1S2776. Analysis of 33 additional multiplex families with CMM from several continents provided further evidence for linkage to the 1p22 region, again strongest in families with the earliest mean age at diagnosis. A nonparametric ordered sequential analysis was used, based on the average age at diagnosis in each family. The highest LOD score, 6.43, was obtained at D1S2779 and occurred when the 15 families with the earliest ages at onset were included. These data provide significant evidence of a novel susceptibility gene for CMM located within chromosome band 1p22.
UR - http://www.scopus.com/inward/record.url?scp=0041664874&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041664874&partnerID=8YFLogxK
U2 - 10.1086/377140
DO - 10.1086/377140
M3 - Article
C2 - 12844286
AN - SCOPUS:0041664874
SN - 0002-9297
VL - 73
SP - 301
EP - 313
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -