TY - JOUR
T1 - Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach
AU - Mattison, Jenny
AU - Kool, Jaap
AU - Uren, Anthony G.
AU - De Ridder, Jeroen
AU - Wessels, Lodewyk
AU - Jonkers, Jos
AU - Bignell, Graham R.
AU - Butler, Adam
AU - Rust, Alistair G.
AU - Brosch, Markus
AU - Wilson, Catherine H.
AU - Van Der Weyden, Louise
AU - Largaespada, David A.
AU - Stratton, Michael R.
AU - Futreal, P. Andy
AU - Van Lohuizen, Maarten
AU - Berns, Anton
AU - Collier, Lara S.
AU - Hubbard, Tim
AU - Adams, David J.
PY - 2010/2/1
Y1 - 2010/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=76249091589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76249091589&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-09-1737
DO - 10.1158/0008-5472.CAN-09-1737
M3 - Article
C2 - 20103622
AN - SCOPUS:76249091589
SN - 0008-5472
VL - 70
SP - 883
EP - 895
JO - Cancer Research
JF - Cancer Research
IS - 3
ER -
