@article{e4d10cd41035466ba8fa34c456394a38,
title = "ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs",
abstract = "Small cell lung carcinoma (SCLC) is a high-grade pulmonary neuroendocrine tumor. The transcription factors ASCL1 and NEUROD1 play crucial roles in promoting malignant behavior and survival of human SCLC cell lines. Here, we find that ASCL1 and NEUROD1 identify heterogeneity in SCLC, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, and NFIB while NEUROD1 targets MYC. ASCL1 and NEUROD1 regulate different genes that commonly contribute to neuronal function. ASCL1 also regulates multiple genes in the NOTCH pathway including DLL3. Together, ASCL1 and NEUROD1 distinguish heterogeneity in SCLC with distinct genomic landscapes and distinct gene expression programs.",
author = "Borromeo, {Mark D.} and Savage, {Trisha K.} and Kollipara, {Rahul K.} and Min He and Alexander Augustyn and Osborne, {Jihan K.} and Luc Girard and Minna, {John D.} and Gazdar, {Adi F.} and Cobb, {Melanie H.} and Johnson, {Jane E.}",
note = "Funding Information: We acknowledge Dr. Julien Sage (Stanford University) for generously contributing the Trp53;Rb1;Rbl2 triple-floxed mice at the initiation of this project, Genomic and Microarray Cores at UT Southwestern for the outstanding Next Generation Sequencing service, and Erin Kibodeaux and Svetlana Earnest for excellent technical assistance. We thank Dr. Francois Guillemot for Ascl1 neoFlox mice, Dr. Klaus Nave for Neurod1 Flox mice, and Dr. Andrew Leiter for Neurod1::Cre mice. We appreciate Dr. Hatten{\textquoteright}s laboratory for generously providing lung tissues from Neurod1::GFP and Neurod1::Cre/ROSA26 LSL-GFP mice. Funding for this project was provided by a Technology Development Award (to J.E.J.) from the Cancer Center NCI Spore Grant in Lung Cancer P50CA70907, Cancer Prevention Research Institute of Texas (CPRIT) grants RP110383 and RP140143 (to M.H.C. and J.E.J.), and NIH grant F31 NS705592 (to M.D.B.). Publisher Copyright: {\textcopyright} 2016 The Author(s)",
year = "2016",
month = aug,
day = "2",
doi = "10.1016/j.celrep.2016.06.081",
language = "English (US)",
volume = "16",
pages = "1259--1272",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",
}