Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: an approach to identify candidate genes involved in tumor development.

Details

Serval ID
serval:BIB_51FF66B07994
Type
Article: article from journal or magazin.
Collection
Publications
Title
Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: an approach to identify candidate genes involved in tumor development.
Journal
Genes, chromosomes & cancer
Author(s)
Missiaglia E., Selfe J., Hamdi M., Williamson D., Schaaf G., Fang C., Koster J., Summersgill B., Messahel B., Versteeg R., Pritchard-Jones K., Kool M., Shipley J.
ISSN
1098-2264 (Electronic)
ISSN-L
1045-2257
Publication state
Published
Issued date
06/2009
Peer-reviewed
Oui
Volume
48
Number
6
Pages
455-467
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. They resemble developing skeletal muscle and are histologically divided into two main subtypes; alveolar and embryonal RMS. Characteristic genomic aberrations, including the PAX3- and PAX7-FOXO1 fusion genes in alveolar cases, have led to increased understanding of their molecular biology. Here, we determined the effect of genomic copy number on gene expression levels through array comparative genomic hybridization (CGH) analysis of 13 RMS cell lines, confirmed by multiplex ligation-dependent probe amplification copy number analyses, combined with their corresponding expression profiles. Genes altered at the transcriptional level by genomic imbalances were identified and the effect on expression was proportional to the level of genomic imbalance. Extrapolating to a public expression profiling dataset for 132 primary RMS identified features common to the cell lines and primary samples and associations with subtypes and fusion gene status. Genes identified such as CDK4 and MYCN are known to be amplified, overexpressed, and involved in RMS tumorigenesis. Of the many genes identified, those with likely functional relevance included CENPF, DTL, MYC, EYA2, and FGFR1. Copy number and expression of FGFR1 was validated in additional primary material and found amplified in 6 out of 196 cases and overexpressed relative to skeletal muscle and myoblasts, with significantly higher expression levels in the embryonal compared with alveolar subtypes. This illustrates the ability to identify genes of potential significance in tumor development through combining genomic and transcriptomic profiles from representative cell lines with publicly available expression profiling data from primary tumors.
Keywords
Allelic Imbalance, Cell Line, Tumor, Chromosome Aberrations, Comparative Genomic Hybridization, Female, Gene Dosage, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Proteins/genetics, Oligonucleotide Array Sequence Analysis, Receptor, Fibroblast Growth Factor, Type 1/genetics, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Rhabdomyosarcoma/genetics, Statistics, Nonparametric
Pubmed
Web of science
Create date
26/09/2023 9:53
Last modification date
04/10/2023 14:27
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