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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
Author(s) -
Missiaglia Edoardo,
Selfe Joanna,
Hamdi Mohamed,
Williamson Daniel,
Schaaf Gerben,
Fang Cheng,
Koster Jan,
Summersgill Brenda,
Messahel Boo,
Versteeg Rogier,
PritchardJones Kathy,
Kool Marcel,
Shipley Janet
Publication year - 2009
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20655
Subject(s) - biology , alveolar rhabdomyosarcoma , gene expression profiling , gene , comparative genomic hybridization , carcinogenesis , genetics , gene expression , copy number variation , fusion gene , gene duplication , pax3 , rhabdomyosarcoma , cancer research , sarcoma , transcription factor , genome , pathology , medicine
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. © 2009 Wiley‐Liss, Inc.