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Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (mRNA)

ABSTRACT: Oral cavity squamous cell carcinoma (OSCC) is a disease with extensive morbidity and mortality and few useful molecular targets. Multiplatform integrated genomic analysis was performed in order to identify genomic drivers and molecularly discernible tumor subtypes. mRNA, miRNA and methylation data are all submitted to GEO We measured gene expression of 43 OSCC cases with the Affymetrix Human Exon 1.0 ST Array

ORGANISM(S): Homo sapiens

SUBMITTER: Zhang Jiexin

PROVIDER: S-ECPF-GEOD-41116 | biostudies-other |

REPOSITORIES: biostudies-other

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Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers.

Project description:The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.

| S-EPMC3858325 | biostudies-literature

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (mRNA)

Project description:Oral cavity squamous cell carcinoma (OSCC) is a disease with extensive morbidity and mortality and few useful molecular targets. Multiplatform integrated genomic analysis was performed in order to identify genomic drivers and molecularly discernible tumor subtypes. mRNA, miRNA and methylation data are all submitted to GEO We measured gene expression of 43 OSCC cases with the Affymetrix Human Exon 1.0 ST Array

2013-01-01 | E-GEOD-41116 | biostudies-arrayexpress

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (mRNA)

2013-01-01 | GSE41116 | GEO

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-01 | E-GEOD-41117 | biostudies-arrayexpress

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-01-01 | GSE41117 | GEO

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (microRNA)

Project description:Oral cavity squamous cell carcinoma (OSCC) is a disease with extensive morbidity and mortality and few useful molecular targets. Multiplatform integrated genomic analysis was performed in order to identify genomic drivers and molecularly discernible tumor subtypes. mRNA, miRNA and methylation data are all submitted to GEO We measured microRNA expression of 43 OSCC cases with Agilent Human miRNA microarray rel12.0

2013-01-01 | E-GEOD-41115 | biostudies-arrayexpress

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (methylation)

Project description:Oral cavity squamous cell carcinoma (OSCC) is a disease with extensive morbidity and mortality and few useful molecular targets. Multiplatform integrated genomic analysis was performed in order to identify genomic drivers and molecularly discernible tumor subtypes. mRNA, miRNA and methylation data are all submitted to GEO We measured methylation of 42 OSCC tumors, 2 normal oral epithelial tissues, and 2 normal blood samples with Illumina HumanMethylation450 arrays

2013-01-01 | E-GEOD-41114 | biostudies-arrayexpress

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (methylation)

2013-01-01 | GSE41114 | GEO

Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (microRNA)

2013-01-01 | GSE41115 | GEO

Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung.

Project description:PURPOSE:Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung. EXPERIMENTAL DESIGN:We conducted a meta-analysis of seven independent datasets containing a total of 593 human primary SCC samples to identify consensus candidate drivers in 3q26-29 amplicon. Through integrating protein-protein interaction network information, we further filtered for candidates that may function together in a network. Computationally predicted candidates were validated using RNA interference (RNAi) knockdown and cell viability assays. Clinical relevance of the experimentally supported drivers was evaluated in an independent cohort of 52 lung SCC patients using survival analysis. RESULTS:The meta-analysis identified 20 consensus candidates, among which four (SENP2, DCUN1D1, DVL3, and UBXN7) are involved in a small protein-protein interaction network. Knocking down any of the four proteins led to cell growth inhibition of the 3q26-29-amplified SCC. Moreover, knocking down of SENP2 resulted in the most significant cell growth inhibition and downregulation of DCUN1D1 and DVL3. Importantly, a gene expression signature composed of SENP2, DCUN1D1, and DVL3 stratified patients into subgroups with different response to adjuvant chemotherapy. CONCLUSION:Together, our findings show that SENP2, DCUN1D1, and DVL3 are candidate driver genes in the 3q26-29 amplicon of SCC, providing novel insights into the molecular mechanisms of disease progression and may have significant implication in the management of SCC of the lung.

| S-EPMC3807802 | biostudies-literature

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