Mutation analysis of 24 known cancer genes in the NCI-60 cell line set.
The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.
Ikediobi
Ogechi N
ON
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom. mrs@sanger.ac.uk.
Davies
Helen
H
Bignell
Graham
G
Edkins
Sarah
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Stevens
Claire
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O'Meara
Sarah
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Santarius
Thomas
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Avis
Tim
T
Barthorpe
Syd
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Brackenbury
Lisa
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Buck
Gemma
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Butler
Adam
A
Clements
Jody
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Cole
Jennifer
J
Dicks
Ed
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Forbes
Simon
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Gray
Kristian
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Halliday
Kelly
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Harrison
Rachel
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Hills
Katy
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Hinton
Jonathan
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Hunter
Chris
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Jenkinson
Andy
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Jones
David
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Kosmidou
Vivienne
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Lugg
Richard
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Menzies
Andrew
A
Mironenko
Tatiana
T
Parker
Adrian
A
Perry
Janet
J
Raine
Keiran
K
Richardson
David
D
Shepherd
Rebecca
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Small
Alex
A
Smith
Raffaella
R
Solomon
Helen
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Stephens
Philip
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Teague
Jon
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Tofts
Calli
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Varian
Jennifer
J
Webb
Tony
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West
Sofie
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Widaa
Sara
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Yates
Andy
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Reinhold
William
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Weinstein
John N
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Stratton
Michael R
MR
Futreal
P Andrew
PA
Wooster
Richard
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D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005091:Exons; D017353:Gene Deletion; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006720:Homozygote; D006801:Humans; D009154:Mutation; D022821:RNA Splice Sites
D022821:RNA Splice Sites