Dataset Information

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 PKC?-SOX2 and PKC?-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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7238436 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Liu Yi Y Yin Ning N Wang Xue X Khoor Andras A Sambandam Vaishnavi V Ghosh Anwesha B AB Fields Zoe A ZA Murray Nicole R NR Justilien Verline V Fields Alan P AP

Cell reports 20200101 3

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 ...[more]

PMID: 31968252

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Project description:ObjectiveAlcohol-impaired driving is a significant public safety concern and is highly prevalent among young adults. Considerable research has examined between-person predictors of alcohol-impaired driving, but there has been little research on factors that predict alcohol-impaired driving at the event level. This pilot/feasibility study was designed to identify within-person, event-level predictors of alcohol-impaired driving intentions in the natural environment using an ecological momentary assessment (EMA) design.MethodThirty-six young adult, moderate drinkers (M age = 22.9 years; 72.2% female; M drinks per occasion = 3.2) were recruited from a university area to complete 2 weeks of EMA. They reported on their subjective levels of intoxication, perceived dangerousness of driving, and driving intentions during real-world drinking episodes. Breath alcohol concentrations were collected with a portable breath alcohol analyzer.ResultsEvent-level perceived danger and subjective intoxication most strongly predicted intentions to drive after drinking, such that higher perceived danger and intoxication predicted lower willingness to drive, after adjusting for baseline alcohol-impaired driving attitudes (ps < .001). When we accounted for perceived danger during drinking episodes at the event and person level, baseline attitudes were no longer predictive of willingness to drive. Higher event-level breath alcohol concentration also predicted lower willingness to drive (p = .003).ConclusionsThis study is the first to demonstrate that event-level risks of alcohol-impaired driving can be collected during drinking episodes in the natural environment. Findings indicate that subjective perceptions of intoxication and risk more strongly predict alcohol-impaired driving intentions than objective intoxication. Findings also suggest that event-level perceptions of intoxication and driving risk may be fruitful targets for interventions to reduce alcohol-impaired driving.

Dataset Information

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

Publications

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

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