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UW-OncoPlex Cancer Sequencing Service Combines Hotspot Detection, Exon Analysis

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The University of Washington and the Seattle Cancer Care Alliance announced earlier this month that they are offering a new cancer sequencing service, called UW-OncoPlex, that targets hotspot regions and exons of 194 genes.

UW's Colin Pritchard, who developed the test with Tom Walsh of the university's division of medical genetics in collaboration with UW's Mary-Claire King, told Clinical Sequencing News in an email that UW-OncoPlex relies on a custom target enrichment strategy using Agilent SureSelect, and that the current version of the panel captures about 850 kilobase pairs.

According to the university, the test is designed to accurately detect a wide range of genetic variants, including single nucleotide variants, small insertions and deletions, gene amplifications, and selected gene fusions. Doctors affiliated with SCCA — a regional cancer treatment center that brings together clinicians from Fred Hutchinson Cancer Research Center, UW Medicine, and Seattle Children’s Hospital — have been using the test to help guide treatment since last year.

"The panel was developed based on genes in which there are current 'actionable' mutations that are validated in the literature as biomarkers for targeted therapies or prognosis, and emerging genes that are important for guiding treatment with drugs in clinical trials," Pritchard said. "We focused on capturing hotspot regions of targetable genomic rearrangements, such as ALK-EML4 and ROS1, as well as targeting most or all exons in the 194 genes."

If patients have already been tested for specific gene mutations using single-gene tests, UW-OncoPlex can also be ordered without those targets, according to the university.

Renato Martins, a medical director at both UW and the SCCA who partnered with Pritchard on the design and validation of the test, told CSN this week that the test has already become the standard of care for some of the hospital's patient populations, particularly for lung and colon cancer.

Currently, he said, clinicians are still ordering single-gene tests, for example, for EGFR and ALK fusions in lung cancer, but they are also ordering OncoPlex at the same time. In time, as the turnaround time of the test — currently eight weeks — goes down, he said it would make more sense to skip single-gene tests and order the panel only.

According to Pritchard, UW is currently running the test in a CLIA-certified lab, using Illumina machines — the HiSeq 2500, HiSeq 2000, and MiSeq. However, he said, the group is not married to the technology, and would consider using a different sequencing chemistry if it saw advantages to that in the future.

Unlike some other academic centers and hospitals that have recently debuted targeted cancer sequencing tests using commercial gene panels like Illumina's TrueSeq and Ion Torrent's AmpliSeq, Pritchard said UW decided that it wanted to design its own custom panel.

"We looked carefully at commercial options but found that none of the currently available panels were able to reliably detect copy number variation or gene rearrangements, two of the most important classes of variation for an oncology panel aimed at guiding cancer therapy," he said in his email.

"PCR amplicon sequencing approaches, in addition to having trouble with copy number variation or structural variant detection, also have limitations of scalability," he said. "Also, we recognized that this is a very rapidly moving field with new targets being identified on a weekly basis. A custom design allows rapid updates of the assay to include new mutations that have just been discovered as having clinical utility."

According to Pritchard, the team is already working on validating an update to the current panel, which would be version 3 of the test.

He said the group designed the panel to be potentially applicable to all cancers, but initially focused mostly on non-small cell lung cancer, acute myeloid leukemia, melanoma, and colon cancer because these diseases have many actionable mutations that have been identified, and because the group was working closely with oncologists in these specific areas.

"For the next version of the panel that will be available soon, we have focused on adding more genes that are relevant for prostate cancer," he wrote.

Martins said that he sees the test benefitting both clinicians and researchers. On a patient-by-patient case, the results can help doctors better treat their patients. But as more and more people are tested, he said he also believes the results could help explain the variability within genomically defined groups — for example, why some patients with activating mutations respond to targeted treatments for years, while others respond for only months.

"What governs that is not a random phenomenon," he said. "There are other genes that likely are playing a role in the amount of time that someone is sensitive to therapy, and if that is the case the way we are going to figure it out is though this broader profiling.

"As we get to these smaller populations that are very important to be identified, these tests are going to be key [for enabling clinical trials as well,]" he added.

"When you start dealing with mutations that have a frequency of only one percent, it's hard to design a feasible trial. To send 100 patients to identify just one, imagine the logistics of that."

But the more patients are profiled using broader sequencing approaches, the more may be identified that belong to these relatively rare genomic subgroups.

In that vein, Martins said the UW and SCCA team is in the process of opening a trial targeting BRAF mutations in lung cancer patients. "These are pretty uncommon in lung cancer, but we have already three patients who are candidates for this study by OncoPlex alone. If we didn’t have the test in place, we probably wouldn’t even have the trial," he said.

Pritchard said the amount the group bills for the test varies "depending on the ordering institution," but is around $2,000 to $3,000. Costs are lower if some genes can be skipped because patients have already been tested using more targeted methods like single-gene assays.

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