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Dartmouth Launches AmpliSeq Cancer Panel, Plans Cardiomyopathy, Autism, CF Tests by Year End

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The Dartmouth-Hitchcock Medical Center is now offering Life Technologies' Ion AmpliSeq Cancer Hotspot Panel for its cancer patients with metastatic colon cancer, melanoma, gliomas, and non-small cell lung cancers.

The CLIA-certified and CAP-accredited Molecular Pathology and Translational Research Laboratory within the medical center's department of pathology validated the 50-gene panel on the Ion Torrent PGM last year and has been offering the panel as a clinical test since late last summer, Greg Tsongalis, a professor of pathology at the Dartmouth-Hitchcock Medical Center, told Clinical Sequencing News.

Since validation, the laboratory has run over 400 patient samples, about 80 percent of which have yielded results, Tsongalis said. Of those, 50 to 60 percent are actionable. In around 30 percent of cases, "we're finding mutations in genes where we're not sure if they're going to be actionable." Turnaround time for the test is one week to 10 days.

Sequence data is kept in a database, so that when new drugs become available or clinical trials open up, the patient's data can be revisited, Tsongalis said.

All patients with the specified indications are automatically tested, Tsongalis said. The laboratory bills patients' insurance companies for the clinically actionable known mutations that are regularly reimbursed as single-gene tests. For instance, he said, in non-small cell lung cancer, testing for mutations in EGFR and the BRAF genes are reimbursable, while the gliomas have a different set of genes that the lab bills payors.

Prior to running the AmpliSeq panel, the laboratory had been testing for those mutations individually with PCR-based assays. "Those were costing us a lot of money," Tsongalis said. The AmpliSeq panel "allowed us to consolidate all our different tests into one."

Tsongalis said he does not yet have data on reimbursement rates for the AmpliSeq panel, but he anticipates that in the long run, the panel will be more cost-effective than the PCR-based assays.

Aside from obtaining reimbursement, another challenge of running clinical next-gen sequencing tests is analysis and annotation, Tsongalis said. Currently the laboratory is using analysis from Golden Helix and Spotfire, but it is also evaluating SoftGenetics.

By the end of the month, the laboratory plans to run the AmpliSeq panel on metastatic breast cancer and will also expand into leukemia and lymphoma in the next few months. "I suspect by the end of this year, every one of our tumor samples will be run on this or some other panel," Tsongalis said.

Recently, the Dartmouth-Hitchcock Medical Center published its validation of the AmpliSeq panel in the journal Clinical Chemistry and Laboratory Medicine.

The main challenge in validating the assay was to obtain samples that were representative of the types of samples the laboratory would be analyzing in the clinic, Tsongalis said. "We had to make sure we had adequate specimen types that were paraffin-embedded," he said, which often involved "taking cell lines with known mutations and embedding them."

The test was validated on the PGM's 316 chip. The limit of detection was determined to be 5 percent for SNVs and 20 percent for insertions and deletions. Tsongalis said that the researchers had to make very few tweaks to the AmpliSeq assay itself, as it was "pretty robust" out of the box.

Currently, he said that the laboratory does not have plans to expand the number of genes for which it screens. "For now, we're staying with the smaller panel until we see some more convincing data on other genes we should include."

Also this year, the laboratory plans to launch clinical panels for other genetic diseases, including cystic fibrosis, autism, and cardiomyopathies.

Aside from a PGM, the laboratory also has Illumina's MiSeq system, and Tsongalis said that he anticipates some of the panels for genetic diseases would be run on that platform. He also said the laboratory is considering bringing on board the MiSeqDx system, which was recently cleared by the US Food and Drug Administration, and replacing the lab's cystic fibrosis screening assay with Illumina's FDA-cleared version that analyzes 139 known pathogenic variants. Tsongalis said the lab would continue to run its in-house developed cystic fibrosis diagnostic assay, which sequences the entire CFTR gene.

Even if the lab does decide to convert to the FDA-cleared MiSeqDx system, Tsongalis does not anticipate trying to bring Dartmouth-Hitchcock's own assays developed on the platform through FDA clearance. "I'm not sure that as a clinical lab, we'd bring [our own] assays through FDA clearance, but we'd be able to run those as [laboratory-developed tests] as long as we do validation and have performance data," he said.

Looking ahead, Tsongalis said that within the next couple of years the lab will be doing exome sequencing routinely for both cancer and genetic disorders.

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