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Series GSE29230 Query DataSets for GSE29230
Status Public on Nov 22, 2011
Title Progressive genomic instability in the FVB/KrasLA2 mouse model of lung cancer
Organism Mus musculus
Experiment type Genome variation profiling by genome tiling array
Summary Alterations in DNA copy number contribute to the development and progression of cancers and are common in epithelial tumors. We have used array Comparative Genomic Hybridization (aCGH) to visualize DNA copy number alterations across the genomes of lung tumors in the KrasLA2 model of lung cancer. Copy number gain involving the Kras locus, as focal amplification or whole chromosome gain, is the most common alteration in these tumors, and with a prevalence that increased significantly with increasing tumor size. Furthermore, Kras amplification was the only major genomic event among the smallest lung tumors, suggesting that this alteration occurs early during the development of mutant Kras driven lung cancers. Recurring gains and deletions of other chromosomes occur progressively more frequently among larger tumors. These results are in contrast to a previous aCGH analysis of lung tumors from KrasLA2 mice on a mixed genetic background, in which relatively few DNA copy alterations were observed regardless of tumor size. Our model features the KrasLA2 allele on the inbred FVB/N mouse strain, and in this genetic background there is a highly statistically significant increase in level of genomic instability with increasing tumor size. These data suggest that recurring DNA copy alterations are important for tumor progression in the KrasLA2 model of lung cancer, and that the requirement for these alterations may be dependent on the genetic background of the mouse strain.
Overall design The KrasLA2 allele, originally on a C57BL6/129svJae mixed background, was backcrossed into the FVB/N background for more than 10 generations in order to minimize the effect of genetic heterogeneity on lung tumor development. Mice were sacrificed at 6 months of age.
Contributor(s) To MD, Quigley DA, Mao J, Del Rosario R, Hsu J, Hodgson G, Jacks T, Balmain A
Citation(s) 21807965
Submission date May 11, 2011
Last update date Mar 23, 2012
Contact name David Quigley
Organization name UCSF
Department Helen Diller Comprehensive Cancer Center
Lab Ashworth Lab
Street address 1450 Third St. Room 207
City San Francisco
State/province CA
ZIP/Postal code 94158
Country USA
Platforms (1)
GPL13520 UCSF_MouseArray_1.0_972 [BAC array]
Samples (83)
GSM722865 CGH_TO_2645g_1056h_49R
GSM722866 CGH_TO_2167m3_1056b_29R
GSM722867 CGH_TO_2167m5_1056b_29L
BioProject PRJNA139937

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