Dataset Information

Comparison of gene expression patterns of two SCLC genetically-engineered mouse models; Rb1 floxed, Trp53 floxed, LSL-Myc T58A-IRES-Luc vs. Rb1 floxed, Trp53 floxed, Rbl2 (p130) floxed

ABSTRACT: Myc expression cooperates with Rb1 and Trp53 loss in mouse lungs to generate rapid, aggressive, highly metastatic and neuroendocrine-low tumors that are similar to human variant subset of SCLC with high NEUROD1 expression. Targeted drug screening reveals that mouse and human MYC-driven SCLC are vulnerable to Aurora kinase inhibition in combination with chemotherapy in vivo. Overall design: Tumor formation is induced by infecting the conditional Rb1 fl/fl; Trp53 fl/fl, LSL-Myc (T58A) and Rb1 fl/fl; Trp53 fl/fl, p130 fl/fl GEMMs with adenoviruses with Cgrp promoter driving Cre recombinase. The tumors were macro-dissected from lungs. RNA was extracted from fresh or flash frozen tumors and subjected to single end RNA sequencing.

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Trudy Oliver

PROVIDER: GSE89660 | GEO | 2017-01-12

SECONDARY ACCESSION(S): PRJNA352851

REPOSITORIES: GEO

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Publications

MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition.

Mollaoglu Gurkan G Guthrie Matthew R MR Böhm Stefanie S Brägelmann Johannes J Can Ismail I Ballieu Paul M PM Marx Annika A George Julie J Heinen Christine C Chalishazar Milind D MD Cheng Haixia H Ireland Abbie S AS Denning Kendall E KE Mukhopadhyay Anandaroop A Vahrenkamp Jeffery M JM Berrett Kristofer C KC Mosbruger Timothy L TL Wang Jun J Kohan Jessica L JL Salama Mohamed E ME Witt Benjamin L BL Peifer Martin M Thomas Roman K RK Gertz Jason J Johnson Jane E JE Gazdar Adi F AF Wechsler-Reya Robert J RJ Sos Martin L ML Oliver Trudy G TG

Cancer cell 20170112 2

Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SC ...[more]

PMID: 28089889

Dataset Information

Comparison of gene expression patterns of two SCLC genetically-engineered mouse models; Rb1 floxed, Trp53 floxed, LSL-Myc T58A-IRES-Luc vs. Rb1 floxed, Trp53 floxed, Rbl2 (p130) floxed

Publications

MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition.

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