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Brain Tumor Clinic to Use SOLiD to Study Expression, Epigenomics in Patient Samples

Researchers at the Center for Advanced Brain Tumor Treatment of the Swedish Medical Center in Seattle plan to use an Applied Biosystems SOLiD sequencer to characterize brain tumors that come to the lab directly from the clinic.
The center, which opened its doors earlier this year, acquired its SOLiD system this month and plans to use it to characterize transcriptional networks and epigenetic modifications in brain cancer. Next year, the system, which has not yet been installed, is also scheduled to replace whole-genome microarrays that the center currently uses for gene-expression analyses.
The CABTT, which is part of the Swedish Neuroscience Institute, provides treatment for both benign and malignant brain tumors at its brain tumor clinic. But the center is “rather unique” in that “the patients that are taken care of are literally right across the hallway from the genomic laboratory,” according to CABTT Director Greg Foltz, a neurosurgeon.
That laboratory currently obtains every brain tumor that is surgically removed at the center and profiles its gene expression using Applied Biosystems’ 1700 Gene Expression Array System microarrays.
That profile is then compared to a gene signature that the researchers have defined based on their own data and those from other studies. That gene signature is correlated to therapeutic response and patient survival. Based on a patient’s profile, doctors can then decide how often to scan for tumor recurrence, or how soon to progress to second-line therapy, according to Foltz.
Over the course of the next year, the center plans to switch completely from gene-expression microarrays to the SOLiD system. Part of the reason is that starting in January, the ABI 1700 arrays will no longer be available because the company last fall decided to phase out the system.
At the time, ABI said it had concluded that the SOLiD was a better platform for providing gene-expression data than hybridization-based microarrays (see In Sequence sister publication BioArray News 10/30/2007).
Better data is in fact what persuaded CABTT to go with a sequencing-based system, rather than a different microarray platform. “The reason we are switching to next-generation [sequencing] is because it has much better sensitivity compared to microarrays,” said Anup Madan, head of the genomics laboratory at CABTT. Using microarrays, he said, “you cannot detect low-level genes, which we think are going to play a major role in telling us about disease progression.”
The reason the center chose ABI’s SOLiD platform rather than a competing system was “our previous relationship” with the company, he said, as well as advantages of the system, including a low error rate.
According to Foltz, the center also plans to use the machine for ChIP-sequencing studies to define transcriptional networks and epigenetic modifications in brain cancer cells.

“The patients that are taken care of are literally right across the hallway from the genomic laboratory.”

In addition to characterizing brain tumors by array- and sequencing-based approaches, the center is collaborating with the Allen Institute for Brain Science to use in situ hybridization to generate an anatomic atlas of gene expression in glioblastoma.
However, the center does not plan to sequence the genomes of brain tumor samples, leaving that up to large-scale efforts such as the National Institute of Health’s Cancer Genome Atlas.
“We certainly are very interested in what’s going on with the Cancer Genome Atlas, and if there is a time in which we can do some exon sequencing to look at mutations in these patients’ tumors … we certainly would use next-generation sequencing as a platform for that,” Foltz said.
Last month, the TCGA Research Network published a study in which it analyzed glioblastoma samples from about 100 patients by sequencing approximately 600 genes, and studied DNA copy number changes, gene expression, and DNA methylation in 206 glioblastoma samples (see In Sequence 9/9/2008).
Separately last month, researchers at Johns Hopkins University published findings of a study in which they analyzed the sequences of 21,000 genes in 22 glioblastoma samples. That project also studied amplifications, deletions, and gene-expression profiles in these samples.
Right now, CABTT is developing a data-analysis pipeline as it waits for ABI to install the SOLiD. Madan, who in the past headed a sequencing group at the Institute for Systems Biology, expects there will be a “learning curve in the next few months, but beginning in 2009, I think we should be able to start using it more routinely to analyze patient [samples].”
At the moment, CABTT’s lab cannot charge insurance companies or patients for the analysis, he said, but it plans to do so once it has gained CLIA approval, which it is in the process of obtaining. A foundation provides funding for patients who cannot afford to pay, he added.
Madan estimated that the analysis will cost no more than $500 per sample, including approximately $200 for supplies.
The plan is to test old samples first that have already been characterized by microarrays, and to compare those data with gene-expression and ChIP-Seq data generated on the SOLiD system.
In later studies, he and his colleagues want to combine gene-expression results with ChIP-Seq data in order “to identify how the epigenetics layer dictates which genes are differentially expressed in these tumor samples, compared to normal samples.”
Before opening the center, Foltz said he and his colleagues saw about 200 brain cancer patients per year. At CABTT, which was established with more than $3.5 million in largely philanthropic funding, he hopes this number will increase.

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