NEW YORK (GenomeWeb) — As Myriad Genetics transitions its hereditary cancer testing business from cancer-type specific Sanger sequencing assays to a single universal next-generation sequencing panel, the company has developed a streamlined laboratory workflow that customizes and automates key steps of the sample prep process, GenomeWeb learned during a recent visit to Myriad's molecular diagnostics laboratories in Salt Lake City.
Predictive testing for hereditary cancer still accounts for the bulk of Myriad's business: During the first quarter of this year, the company booked $159 million in revenue from hereditary cancer testing, 88 percent of its total revenue of $180 million.
Of those revenues, $81.6 million, or 51 percent, came from the myRisk Hereditary Cancer test, an NGS panel Myriad launched last year to eventually replace its older predictive cancer tests, such as BRACAnalysis, Colaris and Colaris AP, Melaris, and Panexia.
Historically, most of its revenue from these tests stemmed from BRACAnalysis, which accounted for about two-thirds of the firm's total revenue in fiscal year 2014.
While Myriad's older hereditary cancer tests focus on specific cancer types, and only analyze one or a few genes, myRisk covers breast, ovarian, colon, uterine, pancreatic, prostate, and gastric cancer, as well as melanoma, and includes 25 genes.
As of the end of the quarter, myRisk's contribution to Myriad's hereditary cancer testing business had grown to 58 percent, and the company said it is on track to transition to myRisk completely by this summer.
Myriad faces competition for myRisk, which has a list price of $4,000, from multiple players that have entered the market with their own multi-gene NGS hereditary cancer panels, including Invitae, Ambry Genetics, and others, who offer their tests for as little as $250.
In the meantime, Myriad has established a streamlined workflow for its molecular diagnostic testing business. Its average turnaround time for myRisk is less than 21 days at the moment, while 95 percent of single-syndrome tests have a turnaround time of fewer than 10 days, and the typical turnaround time for BRACAnalysis is five to seven days. The goal is to reduce the turnaround time for myRisk to 10 days or less by 2016, which would allow doctors to review the results prior to their patients' surgery, which usually requires a turnaround time of two weeks at most.
The company does not disclose its hereditary cancer testing volume but has said previously that it runs 200,000 tests per year, which includes other types of tests.
On a typical day at Myriad's diagnostic laboratories, more than 1,000 barcoded patient samples arrive at the company's accessioning lab in two FedEx shipments per day, one from the firm's East coast and one from its West coast sorting center. Most samples are either blood draws or buccal samples. BRACAnalysis, for example, can be performed from either sample type, while myRisk currently requires a blood draw, though Myriad is working on making it compatible with buccal samples.
Samples are manually transferred to new tubes for DNA extraction, for which Myriad uses customized versions of Qiagen's QIAsymphony platform. The company uses its own wash solution, and each instrument can process up to 24 samples per two-hour run.
This is followed by DNA quantification on Freedom EVO liquid-handling platforms from Tecan. Myriad developed its own pipette tips with a special coating for these and conducts reactions under oil to prevent evaporation, which can be a problem at Salt Lake City's high altitude.
DNA samples are stored for 60 days — a requirement by some US states — in one of two Universal LabStore storage systems from Nexus Biosystems, now part of Brooks Automation, that each have a capacity of 500,000 samples.
Myriad uses the RainDance ThunderStorm platform to set up picodroplet PCR reactions for target amplification prior to sequencing. Two years ago, the two firms signed a multi-year supply agreement, and Myriad currently has more than 30 ThunderStorm instruments in house, allowing it to scale up sample volumes in the future if needed. Each instrument can process up to 24 samples in about 20 hours.
Following PCR amplification, the gene targets then undergo a second round of PCR to produce templates for Illumina sequencing. Myriad sequences 23 of the 25 myRisk panel genes on the HiSeq 2500. The other two genes, which require long-range PCR, are sequenced on the Illumina MiSeq.
Each run of the HiSeq 2500, of which Myriad has a dozen, takes about 40 hours in fast mode and can accommodate 96 samples per flow cell, or 192 samples per run.
The company also still maintains 16 Applied Biosystems 3730xl Sanger sequencers, which it uses to confirm pathogenic mutations found by Illumina sequencing and to sequence family members to confirm whether or not they have a specific mutation.
Sequencing runs are monitored for data quality — including quality scores and depth of coverage — before the data move on for analysis and interpretation, which involves Myriad's in-house analysis software and a team of analysts.
Data from each test is reviewed by two analysts to ensure concordance of all variants. For all deleterious and suspected deleterious mutations, confirmatory data are required before reporting. New variants are passed along for review and classification to Myriad's new mutations committee, which includes lab directors, scientists, and genetic counselors. The committee classifies new variants using a documented in-house process that is consistent with guidelines from the American College of Medical Genetics and Genomics.
Based on the results, a team of clinical data specialists then generates a report that also factors in clinical information provided by the patient's doctor. In-house molecular lab directors sign off on the report before it is sent to the doctor, who can either download it through a secure online portal or have it sent via FedEx. Myriad also has genetic counselors on staff to provide further explanation of the test results to healthcare providers.