Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis

Chen, Sidi; Sanjana, Neville E.; Zheng, Kaijie; Shalem, Ophir; Lee, Kyungheon; Shi, Xi; Scott, David A.; Song, Jun; Pan, Jen Q.; Weissleder, Ralph; Lee, Hakho; Zhang, Feng; Sharp, Phillip A.

doi:10.1016/j.cell.2015.02.038

Advanced Search

Select up to three search categories and corresponding keywords using the fields to the right. Refer to the Help section for more detailed instructions.

Search our Collections & Repository

Advanced Search
Custom Query

All these words:

For very narrow results

This exact word or phrase:

When looking for a specific result

Any of these words:

Best used for discovery & interchangable words

None of these words:

Recommended to be used in conjunction with other fields

Language:

Dates

Publication Date Range:

to

Document Data

Title:

Document Type:

Library

Collection:

Series:

People

Author:

Clear All

Query Builder

Query box

Clear All

For additional assistance using the Custom Query please check out our Help Page

i

Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis

3 12 2015
By Chen, Sidi ; Sanjana, Neville E. ; Zheng, Kaijie ; ...
http://dx.doi.org/10.1016/j.cell.2015.02.038
Source: Cell. 2015; 160(6):1246-1260

[PDF-2.36 MB]

English

Details Supporting Files You May Also Like

Details:

Alternative Title:

Cell
Personal Author:

Chen, Sidi ; Sanjana, Neville E. ; Zheng, Kaijie ; Shalem, Ophir ; Lee, Kyungheon ; ... More +

Chen, Sidi ; Sanjana, Neville E. ; Zheng, Kaijie ; Shalem, Ophir ; Lee, Kyungheon ; Shi, Xi ; Scott, David A. ; Song, Jun ; Pan, Jen Q. ; Weissleder, Ralph ; Lee, Hakho ; Zhang, Feng ; Sharp, Phillip A. Less -
Description:

Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library with 67,405 single-guide RNAs (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage primary tumors were found to target a small set of genes, suggesting that specific loss-of-function mutations drive tumor growth and metastasis. Individual sgRNAs and a small pool of 624 sgRNAs targeting the top-scoring genes from the primary screen dramatically accelerate metastasis. In all of these experiments, the effect of mutations on primary tumor growth positively correlates with the development of metastases. Our study demonstrates Cas9-based screening as a robust method to systematically assay gene phenotypes in cancer evolution in vivo.
Subjects:

[+]

Animals Carcinoma, Non-Small-Cell Lung CRISPR-Cas Systems Gene Knockout Techniques Genome-Wide Association Study Humans Lung Neoplasms Mice Neoplasm Metastasis RNA, Guide, CRISPR-Cas Systems
Keywords:

[+]

Cancer Evolution CRISPR/Cas9 Genome-wide Screen Metastasis
Source:

Cell. 2015; 160(6):1246-1260
Pubmed ID:

25748654
Pubmed Central ID:

PMC4380877
Document Type:

Journal Article
Funding:

R01-CA133404/CA/NCI NIH HHSUnited States/ ; U54 CA151884/CA/NCI NIH HHSUnited States/ ; K99 HG008171/HG/NHGRI NIH HHSUnited States/ ; 5DP1-MH100706/DP/NCCDPHP CDC HHSUnited States/ ; P01 CA042063/CA/NCI NIH HHSUnited States/ ; ... More +

R01-CA133404/CA/NCI NIH HHSUnited States/ ; U54 CA151884/CA/NCI NIH HHSUnited States/ ; K99 HG008171/HG/NHGRI NIH HHSUnited States/ ; 5DP1-MH100706/DP/NCCDPHP CDC HHSUnited States/ ; P01 CA042063/CA/NCI NIH HHSUnited States/ ; P30 CA014051/CA/NCI NIH HHSUnited States/ ; P30-CA14051/CA/NCI NIH HHSUnited States/ ; K99-HG008171/HG/NHGRI NIH HHSUnited States/ ; R01 CA133404/CA/NCI NIH HHSUnited States/ ; DP1 MH100706/MH/NIMH NIH HHSUnited States/ ; R01 DK097768/DK/NIDDK NIH HHSUnited States/ ; 5R01-DK097768/DK/NIDDK NIH HHSUnited States/ Less -
Volume:

160
Issue:

6
Collection(s):

CDC Public Access
Main Document Checksum:

[+]

urn:sha256:e520d794b2ced3fd2f60830d454bf01300f97543acd0d067322ba9b94420e027
Download URL:

https://stacks.cdc.gov/view/cdc/30747/cdc_30747_DS1.pdf
File Type:

	NIHMS666944-supplement-3.pdf	pdf
	NIHMS666944-supplement-4.pdf	pdf
	NIHMS666944-supplement-5.pdf	pdf
	NIHMS666944-supplement-6.pdf	pdf
	NIHMS666944-supplement-7.pdf	pdf
	NIHMS666944-supplement-8.pdf	pdf
	NIHMS666944-supplement-9.docx	docx
	nihms666944.nxml	xml
	nihms666944f1.gif	gif
	nihms666944f1.jpg	jpeg
	NIHMS666944-supplement-1.docx	docx
	nihms666944f2.gif	gif
	nihms666944f2.jpg	jpeg
	nihms666944f3.gif	gif
	nihms666944f3.jpg	jpeg
	nihms666944f4.gif	gif
	nihms666944f4.jpg	jpeg
	nihms666944f5.gif	gif
	nihms666944f5.jpg	jpeg
	nihms666944f6.gif	gif
	nihms666944f6.jpg	jpeg
	NIHMS666944-supplement-10.xlsx	xlsx
	nihms666944f7.gif	gif
	nihms666944f7.jpg	jpeg
	NIHMS666944-supplement-11.xlsx	xlsx
	NIHMS666944-supplement-12.xlsx	xlsx
	NIHMS666944-supplement-13.xlsx	xlsx
	NIHMS666944-supplement-14.xlsx	xlsx
	NIHMS666944-supplement-15.xlsx	xlsx
	NIHMS666944-supplement-2.pdf	pdf

More +