Application of comparative genomic hybridization, spectral karyotyping, and microarray analysis in the identification of subtype-specific patterns of genomic changes in rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) in children occurs predominantly as two major histologically defined subtypes called embryonal RMS (RMS-E) and the prognostically less favorable alveolar RMS (RMS-A). Comparative genomic hybridization (CGH) was performed on 21 RMS and identified consistent gains affecting chromosomes 2 (8/10), 5 (5/10), 6 (3/10), 7 (7/10), 8 (9/10), 11 (6/ 10), and 12 (5/10) in RMS-E. Losses/deletions involved chromosomes 19 (2/10) and chromosomes 4, 9, 10, 17, 21 (1/10 each). High copy number amplification, involving the 2p24 region (5/11) and less frequently, the 12q13-21 (2/11), 9p22 (1/11), and 17q22-25 (1/11) regions, was detected in RMS-A. Gene amplification at band 2p24 was present in 6/12 alveolar tumors, and in each case, MYCN was amplified, together with the distally placed DDX1 gene. For these patients there was a shorter disease free interval and a higher mortality than patients with tumors without amplification. Detailed spectral karyotype analysis (SKY) was performed on two RMS cell lines (one of each subtype) and identified a surprisingly high level of structural change. Gene expression studies with the Atlas Human Cancer Array (588 genes) showed that 153 genes generated a signal of similar intensity in both cell lines, and 45 genes appeared to have subtype-specific expression. The chromosomal location of differentially expressed genes was compared to the pattern of genomic alteration in RMS as determined by CGH in this study and the literature.
Department of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
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A
Pandita
M
M
Zielenska
P
P
Thorner
J
J
Bayani
R
R
Godbout
M
M
Greenberg
J A
JA
Squire
D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000032:analysis; D005784:Gene Amplification; D006801:Humans; D007621:Karyotyping; D009693:Nucleic Acid Hybridization; D012208:Rhabdomyosarcoma / Q000235:genetics*
D018076:DNA, Complementary