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Updated: Aug 24, 2026

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant
Brett G Masayesva1, Patrick Ha, Elizabeth Garrett-Mayer
1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205, USA.
Abstract:
In solid tumors, the relationship between DNA copy number and global expression over large chromosomal regions has not been systematically explored. We used a 12,626-gene expression array analysis of head and neck squamous cell carcinoma and normal oral mucosa and annotated gene expression levels to specific chromosomal loci. Expression alterations correlated with reported data using comparative genomic hybridization. When genes with significant differences in expression between normal and malignant lesions, as defined by significance analysis of microarrays (SAM), were compared to nonsignificant genes, similar chromosomal patterns of alteration in expression were noted. Individual tumors underwent microsatellite analysis and chi(2) analysis of expression at 3p and 22q. Significant 3p underexpression and 22q overexpression were found in all primary tumors with 3p and 22q allelic imbalance, respectively, whereas no tumor without allelic imbalance on these chromosomal arms demonstrated expression differences. Loss and gain of chromosomal material in solid cancers can alter gene expression over large chromosomal regions, including multiple genes unrelated to malignant progression.
Insights
DNA copy number changes in solid tumors significantly impact gene expression across large chromosomal regions. This study links allelic imbalance on chromosomes 3p and 22q to specific expression alterations in head and neck cancers.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- The correlation between DNA copy number alterations and gene expression across extensive chromosomal segments in solid tumors remains underexplored.
- Head and neck squamous cell carcinoma (HNSCC) presents a model for investigating these genomic and transcriptomic relationships.
Purpose of the Study:
- To systematically analyze the relationship between DNA copy number and gene expression across large chromosomal regions in HNSCC.
- To determine if chromosomal allelic imbalance directly influences gene expression levels in malignant lesions.
Main Methods:
- Utilized a 12,626-gene expression array to analyze HNSCC and normal oral mucosa.
- Annotated gene expression data to specific chromosomal loci.
- Performed microsatellite and chi-squared analyses on chromosomes 3p and 22q for allelic imbalance and expression correlation.
Main Results:
- Expression alterations correlated with comparative genomic hybridization data.
- Significant underexpression at 3p and overexpression at 22q were observed in tumors with corresponding allelic imbalance.
- No significant expression differences were found in tumors lacking allelic imbalance on these specific chromosomal arms.
Conclusions:
- Loss and gain of chromosomal material in solid tumors can broadly affect gene expression over large regions.
- Chromosomal instability directly drives gene expression changes, impacting multiple genes, irrespective of their direct role in cancer progression.
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