Chromosome 3q26 Gain Is an Early Event Driving Coordinated Overexpression of the PRKCI, SOX2, and ECT2 Oncogenes in Lung Squamous Cell Carcinoma

• DOI: 10.1016/j.celrep.2019.12.071
• Publication Date: 2020-01-21T15:39:18Z
• Authors: Yi Liu; Ning Yin; Xue Wang; Andras Khoor; Vaishnavi Sambandam; Anwesha B. Ghosh; Zoe A. Fields; Nicole R. Murray; Verline Justilien; Alan P. Fields
• Keywords: Tumor progression

Lung squamous cell carcinoma (LSCC) is a prevalent form of lung cancer exhibiting distinctive histological and genetic characteristics. Chromosome 3q26 copy number gain (CNG) hallmark LSCC present in >90% tumors. We report that CNGs occur early tumorigenesis, persist during tumor progression, drive coordinate overexpression PRKCI, SOX2, ECT2. Overexpression ECT2 the context Trp53 loss sufficient to transform mouse basal stem cells into tumors with genomic features LSCC. Functionally, PRKCI SOX2 collaborate activate an extensive transcriptional program enforces lineage-restricted phenotype, whereas promote oncogenic growth. Gene signatures indicative PKCι-SOX2 PKCι-ECT2 signaling activity are enriched classical subtype human predict distinct therapeutic vulnerabilities. Thus, oncogenes represent multigenic driver