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.
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http://dx.doi.org/10.1016/j.celrep.2019.12.071 | DOI Listing |
Curr Oncol
July 2021
Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, ON P6B 0A8, Canada.
Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, . The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer.
View Article and Find Full Text PDFInt J Mol Sci
March 2021
Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Squamous cell carcinomas of the lung, head and neck, esophagus, and cervix account for more than two million cases of cancer per year worldwide with very few targetable therapies available and minimal clinical improvement in the past three decades. Although these carcinomas are differentiated anatomically, their genetic landscape shares numerous common genetic alterations. Amplification of the third chromosome's distal portion (3q) is a distinguishing genetic alteration in most of these carcinomas and leads to copy-number gain and amplification of numerous oncogenic proteins.
View Article and Find Full Text PDFBull Exp Biol Med
January 2021
National Medical Research Oncology Center, Ministry of Health of the Russian Federation, Rostov-on-Don, Russia.
We analyzed the peculiarities of the copy number variation of genes that regulate apoptosis, DNA repair, cell proliferation, metabolism, and estrogen reception in tumor and normal cells of high-grade and low-grade serous adenocarcinoma of the ovaries. Using real-time qPCR method, the relative copy number of 34 genes (BAX, BCL2, TP53, MDM2, CASP9, CASP3, CASP7, CASP8, PRKCI, SOX2, OCT4, PIK3, PTEN, C-MYC, SOX18, AKT1, NOTCH1, BRCA1, BRCA2, EXO1, SCNN1A, KRAS, EGFR, BRAF, CYP1A1, CYP1A2, CYP1B1, CYP19A, ESR1, ESR2, GPER, STS, SULT1A, and SULT1E1) was determined in normal and tumor cells of the ovaries extracted by contactless capture laser microsection from FFPE-blocks of 200 patients. The most typical molecular markers of ovarian serous adenocarcinoma cells were identified: copy number of PIK3CA, BCL2, BAX, CASP3, and CASP8 genes.
View Article and Find Full Text PDFAdv Biol Regul
December 2020
Department of Cancer Cell Biology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA. Electronic address:
PRKCI is frequently overexpressed in multiple human cancers, and PKCι expression is often prognostic for poor patient survival, indicating that elevated PKCι broadly plays an oncogenic role in the cancer phenotype. PKCι drives multiple oncogenic signaling pathways involved in transformed growth, and transgenic mouse models have revealed that PKCι is a critical oncogenic driver in both lung and ovarian cancers. We now report that recurrent 3q26 copy number gain (CNG) is the predominant genetic driver of PRKCI mRNA expression in all major human cancer types exhibiting such CNGs.
View Article and Find Full Text PDFCell Rep
January 2020
Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA. Electronic address:
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.
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