An integrated study of aberrant gene copy number and gene expression in GIST and LMS.
Increased chromosomal instability that alters the gene copy numbers throughout the genome is known to have a role in molecular pathogenesis of tumors. The impact of gene dosage effect to the expression levels of genes in GIST and LMS is unknown. In this paper, we used a combination of array comparative genomic hybridization (aCGH) and gene expression data to gain insights into the interplay of structural and functional changes of the genome in GIST and LMSs. We identified specific target genes that change their expression due to the gene dosage effect. Statistical analysis identified four chromosomal regions, 1p, 14q, 15q, and 22q, where both copy number and mRNA expression were significantly different between the tumor types. Multi-dimensional scaling (MDS) analysis showed that the gene expression profiles of these four regions accurately distinguish GIST and LMS. In addition, the gene dosage sensitive genes in these regions are differently involved in several tumor growth promoting pathways, implying that there are different mechanisms underlying the GIST and LMS carcinogenesis. Integration of aCGH and gene expression data has not only provided insights into how DNA copy number variations affect the gene expression patterns in these cancers, but also proves to be a promising method to choose biologically relevant biomarkers.
Yang
Da
D
Department of Pathology, Sarcoma Medical Oncology The University of Texas M. D. Anderson Cancer Center, Houston Texas, USA.
Ylipaa
Antti
A
Yang
Jilong
J
Hunt
Kelly
K
Pollock
Raphael
R
Trent
Jonathan
J
Yli-Harja
Olli
O
Shmulevich
Ilya
I
Nykter
Matti
M
Zhang
Wei
W
D014408:Biomarkers, Tumor / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007890:Leiomyosarcoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor