Greater coverage

The Erasmus Medical Centre was a major test site for Affymetrix Exon 1.0 ST Array and has previously published a study in Cancer Research on glial tumours using the Affymetrix U133 Plus 2.0 expression arrays (a 3' focused microarray).

According to Peeters, the Exon 1.0 ST array provides greater genome coverage, as well as the possibility of detecting regulatory mechanisms such as exon skipping, intron retention and alternative promoter usage. The Exon array also demonstrated the ability to identify and characterize glial tumour subgroups based on different analyses methods.

"We were able to identify and molecularly separate these subgroups based on both the expression of the exons, as well as the associated transcript expression," she says.

"We were able to detect differentially regulated splice variants, novel exons and possible translocated transcripts and we have also been able to detect exon skipping mutations."

For Pim French, the key goal wasn't to find more markers for specific subtypes of glial brain tumours but to utlise the potential of such arrays to allow researchers to find causal genetic changes, like the pathological splice variant of EGFR.

According to French, a large proportion of glial brain tumours have a genetic deletion within the epidermal growth factor receptor (EGFR) locus.

"This deletion results in the expression of a pathological splice variant that is constitutively active," he says. "This splice variant has been demonstrated to play a role in tumour formation and is associated with response to EGFR inhibitors."

Using the Exon array, "I was most excited to identify pathological splice variants like the one in EGFR. In fact, we found a few in that gene we were not aware of.

"Such pathological splice variants will not be detected with other expression profiling platforms."

"The information contained on the exon array is greater than the older 3' arrays and such genome coverage give more possibility of answering more diverse biological questions," Peeters says. "Having run disease-related samples on the arrays gives endless possibilities of re-mining the data."