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| Status |
Public on Oct 11, 2015 |
| Title |
Clonal evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Human tumours show a high level of clonal heterogeneity that contributes to malignant progression and metastasis, but the processes that influence the timing of metastatic dissemination of subclones are unknown. Here, we have used whole exome sequencing of 98 matched benign, malignant, and metastatic skin tumours from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumour, but then evolve separately, acquiring an additional set of mutations during growth at distant sites. Shared mutations between primary carcinomas and their matched metastases have the distinct A>T signature of the initiating carcinogen Dimethylbanzanthracene (DMBA), but non-shared mutations are primarily G>T or C>T substitutions, associated with oxidative stress. We found recurrent point mutations in several hundred genes, including several in the Ras (Hras, Kras, and Pik3ca) pathway. We propose that carcinogen-driven mouse tumour models can aid our understanding of the forces that shape clonal and genetic evolution of human cancers.
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| Overall design |
Benign, primary, and metastatic DMBA/TPA-initiated tumours and matched dorsal skin from 15 FVBBX mice (Spretus x FVB F1s crossed to FVBs); 9 wild-type and 6 HrasKO mice
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| Contributor(s) |
McCreery M, Quigley DA, Balmain A |
| Citation(s) |
26523969 |
| Submission date |
Dec 08, 2014 |
| Last update date |
Apr 18, 2017 |
| Contact name |
David Quigley |
| Organization name |
UCSF
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| Department |
Helen Diller Comprehensive Cancer Center
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| Lab |
Ashworth Lab
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| Street address |
1450 Third St. Room 207
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (112)
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| Relations |
| BioProject |
PRJNA269625 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63967_RAW.tar |
470.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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