Localization of a novel melanoma susceptibility locus to 1p22
(2003) In American Journal of Human Genetics 73(2). p.301-313- Abstract
- 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... (More)
- 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 [theta] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (theta = 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 13 in this subset, with the highest parametric LOD score, 4.95 (theta = 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. (Less)
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- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Human Genetics
- volume
- 73
- issue
- 2
- pages
- 301 - 313
- publisher
- Cell Press
- external identifiers
-
- pmid:12844286
- wos:000184223900007
- scopus:0041664874
- ISSN
- 0002-9297
- language
- English
- LU publication?
- yes
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- f0c42883-7c86-4a09-9c7b-1502b0530d09 (old id 306191)
- alternative location
- http://www.journals.uchicago.edu/AJHG/journal/issues/v73n2/35058/brief/35058.abstract.html
- date added to LUP
- 2016-04-01 11:35:56
- date last changed
- 2022-02-18 02:07:01
@article{f0c42883-7c86-4a09-9c7b-1502b0530d09,
abstract = {{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 [theta] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (theta = 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 13 in this subset, with the highest parametric LOD score, 4.95 (theta = 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.}},
author = {{Gillanders, E and Juo, SHH and Holland, EA and Jones, M and Nancarrow, D and Freas-Lutz, D and Sood, R and Park, N and Faruque, M and Markey, Christopher and Kefford, RF and Palmer, J and Bergman, W and Bishop, DT and Tucker, MA and Bressac-de Paillerets, B and Hansson, J and Stark, M and Gruis, N and Bishop, JN and Goldstein, AM and Bailey-Wilson, JE and Mann, GJ and Hayward, N and Trent, J}},
issn = {{0002-9297}},
language = {{eng}},
number = {{2}},
pages = {{301--313}},
publisher = {{Cell Press}},
series = {{American Journal of Human Genetics}},
title = {{Localization of a novel melanoma susceptibility locus to 1p22}},
url = {{http://www.journals.uchicago.edu/AJHG/journal/issues/v73n2/35058/brief/35058.abstract.html}},
volume = {{73}},
year = {{2003}},
}