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Series GSE149444 Query DataSets for GSE149444
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
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.
 
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.
 
Contributor(s) Ireland AS, Qiao Y, Huang X, Tarapcsak S, Marth G, Oliver TG
Citation(s) 34016693
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
Phone 6174607487
Organization name Duke University
Department Pharmacology & Cancer Biology
Lab theoliverlab
Street address Duke University, Box 3813, LSRC Room C138B, 308 Research Drive
City Durham
State/province NC
ZIP/Postal code 27708
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (3)
GSM4502393 17686X1 RPM Transition Cells Day 4
GSM4502394 17686X2 RPM Transition Cells Day 23
GSM4502395 17686X3 Matching Blood Normal
This SubSeries is part of SuperSeries:
GSE149180 MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate [SuperSeries]
Relations
BioProject PRJNA628698
SRA SRP258732

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE149444_17686R-mouse-transition-somatic.vcf.gz 4.2 Mb (ftp)(http) VCF
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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