A comparison of CDKN2A mutation detection within the Melanoma Genetics Consortium (GenoMEL).
CDKN2A is the major melanoma susceptibility gene so far identified, but only 40% of three or more case families have identified mutations. A comparison of mutation detection rates was carried out by "blind" exchange of samples across GenoMEL, the Melanoma Genetics Consortium, to establish the false negative detection rates. Denaturing high performance liquid chromatography (DHPLC) screening results from 451 samples were compared to screening data from nine research groups in which the initial mutation screen had been done predominantly by sequencing. Three samples with mutations identified at the local centres were not detected by the DHPLC screen. No additional mutations were detected by DHPLC. Mutation detection across groups within GenoMEL is carried out to a consistently high standard. The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes.
Harland
Mark
M
Division of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Cancer Centre at Leeds, St James's University Hospital, Leeds, UK.
Goldstein
Alisa M
AM
Kukalizch
Kairen
K
Taylor
Claire
C
Hogg
David
D
Puig
Susana
S
Badenas
Celia
C
Gruis
Nelleke
N
ter Huurne
Jeanet
J
Bergman
Wilma
W
Hayward
Nicholas K
NK
Stark
Mitchell
M
Tsao
Hensin
H
Tucker
Margaret A
MA
Landi
Maria Teresa
MT
Scarra
Giovanna Bianchi
GB
Ghiorzo
Paola
P
Kanetsky
Peter A
PA
Elder
David
D
Mann
Graham J
GJ
Holland
Elizabeth A
EA
Bishop
D Timothy
DT
Bishop
Julia Newton
JN
D002851:Chromatography, High Pressure Liquid; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000235:genetics*