Duplication of CXC chemokine genes on chromosome 4q13 in a melanoma-prone family.
Copy number variations (CNVs) have been shown to contribute substantially to disease susceptibility in several inherited diseases including cancer. We conducted a genome-wide search for CNVs in blood-derived DNA from 79 individuals (62 melanoma patients and 17 spouse controls) of 30 high-risk melanoma-prone families without known segregating mutations using genome-wide comparative genomic hybridization (CGH) tiling arrays. We identified a duplicated region on chromosome 4q13 in germline DNA of all melanoma patients in a melanoma-prone family with three affected siblings. We confirmed the duplication using quantitative PCR and a custom-made CGH array design spanning the 4q13 region. The duplicated region contains 10 genes, most of which encode CXC chemokines. Among them, CXCL1 (melanoma growth-stimulating activity α) and IL8 (interleukin 8) have been shown to stimulate melanoma growth in vitro and in vivo. Our data suggest that the alteration of CXC chemokine genes may confer susceptibility to melanoma.
Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, DHHS, MD, USA.
Xiaohong R
XR
Yang
Kevin
K
Brown
Maria T
MT
Landi
Paola
P
Ghiorzo
Celia
C
Badenas
Mai
M
Xu
Nicholas K
NK
Hayward
Donato
D
Calista
Giorgio
G
Landi
William
W
Bruno
Giovanna
G
Bianchi-Scarrà
Paula
P
Aguilera
Susana
S
Puig
Alisa M
AM
Goldstein
Margaret A
MA
Tucker
D000328:Adult; D019743:Chemokines, CXC / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005190:Family; D005260:Female; D020440:Gene Duplication / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics*; D055815:Young Adult
D019743:Chemokines, CXC; D004273:DNA, Neoplasm