@article{acb4178bbc854527ba1608c6b9ed3519,
title = "Chromosome 3q26 Gain Is an Early Event Driving Coordinated Overexpression of the PRKCI, SOX2, and ECT2 Oncogenes in Lung Squamous Cell Carcinoma",
abstract = "Lung squamous cell carcinoma (LSCC) is a prevalent form of lung cancer exhibiting distinctive histological and genetic characteristics. Chromosome 3q26 copy number gain (CNG) is a genetic hallmark of LSCC present in >90% of tumors. We report that 3q26 CNGs occur early in LSCC tumorigenesis, persist during tumor progression, and drive coordinate overexpression of PRKCI, SOX2, and ECT2. Overexpression of PRKCI, SOX2, and ECT2 in the context of Trp53 loss is sufficient to transform mouse lung basal stem cells into tumors with histological and genomic features of LSCC. Functionally, PRKCI and SOX2 collaborate to activate an extensive transcriptional program that enforces a lineage-restricted LSCC phenotype, whereas PRKCI and ECT2 collaborate to promote oncogenic growth. Gene signatures indicative of PKCι-SOX2 and PKCι-ECT2 signaling activity are enriched in the classical subtype of human LSCC and predict distinct therapeutic vulnerabilities. Thus, the PRKCI, SOX2, and ECT2 oncogenes represent a multigenic driver of LSCC.",
keywords = "3q26 copy number gain, CNG, ECT2, LSCC, PRKCI, SOX2, lung basal stem cells, lung squamous cell carcinoma, oncogenic transformation",
author = "Yi Liu and Ning Yin and Xue Wang and Andras Khoor and Vaishnavi Sambandam and Ghosh, {Anwesha B.} and Fields, {Zoe A.} and Murray, {Nicole R.} and Verline Justilien and Fields, {Alan P.}",
note = "Funding Information: We thank Ms. Kayla Lewis, Ms. Capella Weems, and Mr. Jorge Lombardi for technical assistance; Dr. Laura Lewis-Tuffin and the Mayo Clinic Cellular Imaging and Flow Cytometry Facility for assistance with cell sorting; Ms. Brandy Edenfield and the Mayo Clinic Cancer Biology Histology Facility for processing tumor tissues for analysis; and the Mayo Clinic Sequencing Facility for RNA-seq runs. We also acknowledge members of the Fields laboratory for critical feedback on the manuscript. This work was supported by grants from the National Institutes of Health/National Cancer Institute ( R01 CA081436-22 and R01 CA206267-04 to A.P.F.; R01 CA140290-05 to N.R.M.; and R03 CA235189 to V.J.). A.P.F. is the Monica Flynn Jacoby Professor of Cancer Research, an endowment fund that provides partial support for the investigator{\textquoteright}s research program. V.J. was supported in part by a Mayo Clinic Center for Biomedical Discovery Career Development Award and an American Cancer Society Research Scholar Award ( RSG-18-201-01 ). Y.L. and N.Y. are recipients of the Edward C. Kendall Fellowship in Biochemistry from the Mayo Clinic Graduate School . Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2020",
month = jan,
day = "21",
doi = "10.1016/j.celrep.2019.12.071",
language = "English (US)",
volume = "30",
pages = "771--782.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}