Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach.
Comparative genomic hybridization (CGH) can reveal important disease genes but the large regions identified could sometimes contain hundreds of genes. Here we combine high-resolution CGH analysis of 598 human cancer cell lines with insertion sites isolated from 1,005 mouse tumors induced with the murine leukemia virus (MuLV). This cross-species oncogenomic analysis revealed candidate tumor suppressor genes and oncogenes mutated in both human and mouse tumors, making them strong candidates for novel cancer genes. A significant number of these genes contained binding sites for the stem cell transcription factors Oct4 and Nanog. Notably, mice carrying tumors with insertions in or near stem cell module genes, which are thought to participate in cell self-renewal, died significantly faster than mice without these insertions. A comparison of the profile we identified to that induced with the Sleeping Beauty (SB) transposon system revealed significant differences in the profile of recurrently mutated genes. Collectively, this work provides a rich catalogue of new candidate cancer genes for functional analysis.
Mattison
Jenny
J
The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.
Kool
Jaap
J
Uren
Anthony G
AG
de Ridder
Jeroen
J
Wessels
Lodewyk
L
Jonkers
Jos
J
Bignell
Graham R
GR
Butler
Adam
A
Rust
Alistair G
AG
Brosch
Markus
M
Wilson
Catherine H
CH
van der Weyden
Louise
L
Largaespada
David A
DA
Stratton
Michael R
MR
Futreal
P Andy
PA
van Lohuizen
Maarten
M
Berns
Anton
A
Collier
Lara S
LS
Hubbard
Tim
T
Adams
David J
DJ
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization / Q000379:methods*; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D023281:Genomics / Q000379:methods; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D009154:Mutation; D000071317:Nanog Homeobox Protein; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D013045:Species Specificity; D013234:Stem Cells / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D004251:DNA Transposable Elements; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D025521:Tumor Suppressor Proteins