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

Yi Liu, Ning Yin, Xue Wang, Andras Khoor, Vaishnavi Sambandam, Anwesha B. Ghosh, Zoe A. Fields, Nicole R. Murray, Verline Justilien, Alan P. Fields

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)771-782.e6
JournalCell reports
Volume30
Issue number3
DOIs
StatePublished - Jan 21 2020

Keywords

  • 3q26 copy number gain
  • CNG
  • ECT2
  • LSCC
  • PRKCI
  • SOX2
  • lung basal stem cells
  • lung squamous cell carcinoma
  • oncogenic transformation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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