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| Status |
Public on Jan 01, 2024 |
| Title |
Lineage-specific intolerance to oncogenic drivers restricts histological transformation [ATAC-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial cell types in the lung. Intriguingly, LUAD can histologically transform into SCLC following treatment with targeted therapies. Here we designed models to follow the conversion of LUAD to SCLC and found the barrier to histological transformation converges on tolerance to Myc, which we implicate as a lineage-specific driver of the pulmonary neuroendocrine cell. Histological transformations are frequently accompanied by activation of the Akt pathway. Manipulating this pathway permitted tolerance to Myc as an oncogenic driver, producing rare, stem-like cells, transcriptionally resembling the pulmonary basal lineage. These findings suggest histological transformation may require the plasticity inherent to the basal stem cell, enabling tolerance to previously incompatible oncogenic driver programs.
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| Overall design |
Bulk ATAC-sequencing was performed for 15 high quality libraries across 8 biological conditions.
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| Contributor(s) |
Gardner EE, Earlie EM, Li K, Thomas J, Hubisz MJ, Stein BD, Zhang C, Cantley LC, Laughney AM, Varmus H |
| Citation(s) |
38330136 |
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| Submission date |
Nov 19, 2023 |
| Last update date |
Apr 02, 2024 |
| Contact name |
Ashley M Laughney |
| E-mail(s) |
ashley.laughney@gmail.com
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| Organization name |
Weill Cornell Medicine
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| Department |
Physiology, Biophysics, and Systems Biology
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| Lab |
Laughney Lab
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| Street address |
413 East 69th Street
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| City |
NEW YORK |
| State/province |
New York |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (15)
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| GSM7908367 |
Lung, PNEC origin, LUAD genotype, chromatin, pooled |
| GSM7908368 |
Lung, de novo SCLC, chromatin, rep 1 |
| GSM7908369 |
Lung, de novo SCLC, chromatin, rep 2 |
| GSM7908370 |
Lung, AT2 origin, SCLC genotype, chromatin, pooled |
| GSM7908371 |
Lung, de novo LUAD, chromatin, rep 1 |
| GSM7908372 |
Lung, de novo LUAD, chromatin, rep 2 |
| GSM7908373 |
Lung, de novo LUAD, chromatin, rep 3 |
| GSM7908374 |
Lung, AT2 origin, WT, chromatin, rep 1 |
| GSM7908375 |
Lung, AT2 origin, WT, chromatin, rep 2 |
| GSM7908376 |
Lung, AT2 origin, Pten loss, chromatin, rep 1 |
| GSM7908377 |
Lung, AT2 origin, Pten loss, chromatin, rep 2 |
| GSM7908378 |
Lung, AT2 origin, Pten E545K, chromatin, rep 1 |
| GSM7908379 |
Lung, AT2 origin, Pten E545K, chromatin, rep 2 |
| GSM7908380 |
Lung, AT2 origin, Pten H1047R, chromatin, rep 1 |
| GSM7908381 |
Lung, AT2 origin, Pten H1047R, chromatin, rep 2 |
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| This SubSeries is part of SuperSeries: |
| GSE248207 |
Lineage-specific intolerance to oncogenic drivers restricts histological transformation |
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| Relations |
| BioProject |
PRJNA1042809 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248206_RAW.tar |
23.8 Mb |
(http)(custom) |
TAR (of BROADPEAK) |
| GSE248206_consensus_peaks.mRp.clN.annotatePeaks.txt.gz |
7.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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