Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide LOH and DNA copy number alteration in HPV-neg OSCC and their associations with disease-specific survival

ABSTRACT: Oral squamous cell carcinoma (OSCC) is associated with high case-fatality. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we examined paired DNA from peripheral blood and tumor cells to assess genome-wide LOH and DNA copy number alteration (CNA) and their associations with risk factors, tumor characteristics, and disease-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p, and 11q that seem to play an important role in oral cancer biology and survival from this disease. We used Affymetrix 6.0 SNP arrays to test paired DNA from peripheral blood and tumor cells isolated by laser capture microdissection from 75 patients with HPV-negative OSCC. Peripheral blood DNA is used as reference for CNA to LOH.

ORGANISM(S): Homo sapiens

SUBMITTER: Chu Chen

PROVIDER: E-GEOD-68717 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-Wide Loss of Heterozygosity and DNA Copy Number Aberration in HPV-Negative Oral Squamous Cell Carcinoma and Their Associations with Disease-Specific Survival.

Chen Chu C Zhang Yuzheng Y Loomis Melissa M MM Upton Melissa P MP Lohavanichbutr Pawadee P Houck John R JR Doody David R DR Mendez Eduardo E Futran Neal N Schwartz Stephen M SM Wang Pei P

PloS one 20150806 8

Oral squamous cell cancer of the oral cavity and oropharynx (OSCC) is associated with high case-fatality. For reasons that are largely unknown, patients with the same clinical and pathologic staging have heterogeneous response to treatment and different probability of recurrence and survival, with patients with Human Papillomavirus (HPV)-positive oropharyngeal tumors having the most favorable survival. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that ...[more]

PMID: 26247464

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Project description:BACKGROUND: Cervical carcinoma develops as a result of multiple genetic alterations. Different studies investigated genomic alterations in cervical cancer mainly by means of metaphase comparative genomic hybridization (mCGH) and microsatellite marker analysis for the detection of loss of heterozygosity (LOH). Currently, high throughput methods such as array comparative genomic hybridization (array CGH), single nucleotide polymorphism array (SNP array) and gene expression arrays are available to study genome-wide alterations. Integration of these 3 platforms allows detection of genomic alterations at high resolution and investigation of an association between copy number changes and expression. RESULTS: Genome-wide copy number and genotype analysis of 10 cervical cancer cell lines by array CGH and SNP array showed highly complex large-scale alterations. A comparison between array CGH and SNP array revealed that the overall concordance in detection of the same areas with copy number alterations (CNA) was above 90%. The use of SNP arrays demonstrated that about 75% of LOH events would not have been found by methods which screen for copy number changes, such as array CGH, since these were LOH events without CNA. Regions frequently targeted by CNA, as determined by array CGH, such as amplification of 5p and 20q, and loss of 8p were confirmed by fluorescent in situ hybridization (FISH). Genome-wide, we did not find a correlation between copy-number and gene expression. At chromosome arm 5p however, 22% of the genes were significantly upregulated in cell lines with amplifications as compared to cell lines without amplifications, as measured by gene expression arrays. For 3 genes, SKP2, ANKH and TRIO, expression differences were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSION: This study showed that copy number data retrieved from either array CGH or SNP array are comparable and that the integration of genome-wide LOH, copy number and gene expression is useful for the identification of gene specific targets that could be relevant for the development and progression in cervical cancer. Keywords: DNA copynumber RNA expression correlation Cervival cancer cell lines were hybridized to Affymetrix Focus arrays in duplicate. Correlations were made with copynumber profiles from arrayCGH and SNP arrays.

Dataset Information

Genome-wide LOH and DNA copy number alteration in HPV-neg OSCC and their associations with disease-specific survival

Publications

Genome-Wide Loss of Heterozygosity and DNA Copy Number Aberration in HPV-Negative Oral Squamous Cell Carcinoma and Their Associations with Disease-Specific Survival.

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