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Status |
Public on May 28, 2020 |
Title |
MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate [WGS data] |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
Distinct SCLC molecular subtypes have been defined based on expression of lineage-related transcription factors: ASCL1, NEUROD1, POU2F3 or YAP1, but their origins remain unknown. To study transcriptional dynamics of MYC-driven tumor evolution and compare transcriptional states to human SCLC tumors, we performed bulk and single-cell RNA-sequencing on various timepoints of Rb1/Trp53/MycT58A (RPM) tumor cells (from Ad-Cgrp-Cre infected mice) as they progress in culture, and on RPM bulk tumors. Here, to complement these analyses we performed ~30X whole-genome sequencing (WGS) of early (day 4) and late (day 23) time-point RPM tumor cells from culture, along with a matching normal blood control to confirm complete loss of expected regions of Rb1 and Trp53. WGS analyses revealed no detectable copy number variations (CNVs), and SNV analysis suggests that minimal clonal and subclonal evolution occurs in vitro. Together, these data ultimately reveal that MYC drives the dynamic evolution of SCLC subtypes. We find that MYC promotes a temporal shift from an ASCL1-to-NEUROD1-to-YAP1+ state from a neuroendocrine cell of origin. MYC activates Notch signaling to dedifferentiate tumor cells to non-neuroendocrine fates. These findings support our overall conclusions that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype.
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Overall design |
~30X WGS data was collected from Day 4 and Day 23 tumor samples, as well as from a blood sample from RPM mice as the normal control.
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Contributor(s) |
Ireland AS, Qiao Y, Huang X, Tarapcsak S, Marth G, Oliver TG |
Citation(s) |
34016693 |
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Submission date |
Apr 27, 2020 |
Last update date |
Sep 12, 2023 |
Contact name |
Trudy Oliver |
E-mail(s) |
tgo@duke.edu, trudy.oliver@duke.edu
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Phone |
6174607487
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Organization name |
Duke University
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Department |
Pharmacology & Cancer Biology
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Lab |
theoliverlab
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Street address |
Duke University, Box 3813, LSRC Room C138B, 308 Research Drive
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City |
Durham |
State/province |
NC |
ZIP/Postal code |
27708 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (3) |
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This SubSeries is part of SuperSeries: |
GSE149180 |
MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate [SuperSeries] |
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Relations |
BioProject |
PRJNA628698 |
SRA |
SRP258732 |
Supplementary file |
Size |
Download |
File type/resource |
GSE149444_17686R-mouse-transition-somatic.vcf.gz |
4.2 Mb |
(ftp)(http) |
VCF |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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