Abstract: | Altered expression of genes can have phenotypic consequences in cancer development and treatment, developmental
abnormalities, and differentiation processes. Here we describe a rapid approach, termed comparative expressed sequence
hybridization (CESH), which gives a genome-wide view of relative expression patterns within tissues according to chromosomal
location. No prior knowledge of genes or cloning is required, and minimal amounts of tissue can be used. Expression profiles
are achieved in a manner similar to the identification of chromosomal imbalances by comparative genomic hybridization
analysis. The approach is demonstrated to indicate a chromosomal region that harbors overexpressed genes that may be
associated with a drug-resistant phenotype. In addition, known and new regions of differential gene expression in both normal
tissues and tumor samples from the soft tissue sarcoma group of rhabdomyosarcoma (RMS) are indicated. These regions included
2p24; overexpression of MYCN at 2p24 was confirmed by quantitative reverse transcription-PCR for all of the alveolar RMS
cases and did not necessarily correspond to genomic amplification. Evidence including region specific microarray analysis
indicated that overexpression of several genes from a region may be required for detection by CESH. This evidence is
consistent with clusters of functionally related genes and mechanisms that affect the expression of a number of genes at a
particular genomic location. The distinctive CESH profiles demonstrated in different subtypes of RMS show potential for tumor
classification. |