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| Status |
Public on Mar 17, 2021 |
| Title |
Characterization of tumor mutational burden in LKB1 mutant lung tumors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Inactivating mutations in LKB1/STK11 are present in ~20% of non-small cell lung cancers (NSCLC) and portend poor response to anti-PD-1 immunotherapy in patients and genetically engineered mouse model (GEMMs). Here, we sought to uncover the basis for immunotherapy resistance of these tumors and to define strategies that overcome this barrier. Whereas high tumor mutational burden (TMB) often correlates with response to anti-PD1 treatment, we found that LKB1-deficient NSCLCs from non-smokers and GEMMs exhibited striking elevations in nonsynonymous mutations compared to LKB1 wildtype tumors. Correspondingly, LKB1 mutant NSCLC cell lines showed defects in both replication dependent and independent double-strand DNA break (DSB) repair, which were reversed upon LKB1 re-expression.
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| |
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| Overall design |
Examine mRNA of KP and KL GEMM lung tumor nodules derived cell lines for mutational burden analysis.
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| Contributor(s) |
Deng J, Wong KK |
| Citation(s) |
34142094 |
| Submission date |
Sep 10, 2019 |
| Last update date |
Jun 19, 2021 |
| Contact name |
Igor Dolgalev |
| Organization name |
NYU Grossman School of Medicine
|
| Street address |
550 1st Ave
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10016 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (11)
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| Relations |
| BioProject |
PRJNA564852 |
| SRA |
SRP221293 |
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