 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 04, 2021 |
| Title |
A functional taxonomy of tumor suppression in oncogenic KRAS-driven lung cancer |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Extensive cancer genotyping has identified a large number of putative tumor suppressor genes. However, genome sequencing data alone is insufficient to uncover the importance or the specific functional roles of these genes during carcinogenesis. It is generally unclear whether more frequently mutated tumor suppressors are also more consequential for tumor development. Furthermore, whether tumor suppressors restrict the rate of tumor growth, decrease the probability of incipient tumorigenesis, or limit the emergence of particularly fast-growing clones remains unknown for even the most well-studied tumor suppressors. Here we use a multiplexed autochthonous mouse model of oncogenic Kras-driven human lung adenocarcinoma to quantify the impact of forty-eight known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We discover many previously understudied functional tumor suppressors that constrain multiple aspects of carcinogenesis in vivo. Inactivation of some genes substantially elevates tumor growth rate, while the inactivation of others increases the probability of tumor initiation and/or the emergence of exceptionally large tumors. While some known and novel functional tumor suppressor genes exert particularly strong effects during specific phases of tumorigenesis, others impact multiple facets of tumor development. These direct and causal analyses uncover an unexpectedly complex functional landscape of tumor suppression. This map of carcinogenesis has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression.
|
| |
|
| Overall design |
We use a multiplexed autochthonous mouse model of oncogenic Kras-driven human lung adenocarcinoma to quantify the impact of forty-eight known and putative tumour suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution.
|
| Web link |
https://pubmed.ncbi.nlm.nih.gov/33608386/
|
| |
|
| Contributor(s) |
Cai H, Chew SK, Li C, Tsai MK, Andrejka L, Murray CW, Hughes NW, Shuldiner EG, Tang R, Hung KL, Chen LC, Lee SC, Yousefi M, McFarland CD, Lin W, Kunder CA, Cong L, Petrov DA, Swanton C, Winslow MM |
| Citation(s) |
33608386 |
| |
| Submission date |
Mar 03, 2020 |
| Last update date |
May 05, 2021 |
| Contact name |
Chuan Li |
| E-mail(s) |
chuanli@stanford.edu
|
| Organization name |
Stanford University
|
| Department |
Biology
|
| Lab |
Dmitri Petrov lab
|
| Street address |
327 Campus Drive
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA610052 |
| SRA |
SRP251451 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE146302_RAW.tar |
9.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...