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Myriad Plans NGS-Based Tests, Says Whole-Genome Sequencing Not Yet Ready for Clinical Use


By Monica Heger

This article has been updated to correct the title of a Myriad official.

Myriad Genetics said that it is moving into the next-generation sequencing space with the development of a suite of diagnostic tests for cancer.

Mark Capone, president of Myriad Genetics Laboratories, outlined the company's strategy on using the technology during a late December conference call hosted by investment bank Jefferies on the evolution of next-gen sequencing in clinical practice.

Among the next-gen-based tests in Myriad's pipeline are a tissue-based BRCA test that will be optimized to screen formalin-fixed paraffin-embedded tissue, a hereditary cancer test, a colon cancer diagnostic test, and an early cancer detection test, said Capone.

A company spokesperson told Clinical Sequencing News that Myriad is currently equipped with several Illumina HiSeqs and MiSeqs, as well as Roche 454s. Additionally, it is considering the Ion Torrent PGM. The spokesperson declined to disclose which machines the tests were being developed on, however.

Capone said during the call that he does not believe that sequencing systems are currently "accurate enough to perform whole-genome or whole-exome sequencing for clinical purposes," but they are "sensitive and specific enough" when used in gene panels.

As such, the company is "investing in R&D to identify additional proprietary content beyond the genes Myriad currently screens," he said.

Currently, the company has nine different tests. Its most well-known, the BRACAnalysis test, screens for mutations in the BRCA 1 and 2 genes, which are predictive of hereditary breast and ovarian cancer. Other tests on the market include its Colaris test for colorectal and uterine cancer; Prolaris for prostate cancer; Melaris for hereditary melanoma; and Prezeon, which assesses the status of the PTEN gene associated with improved drug response in a range of cancers, including breast, colon, prostate, and glioma..

The tissue-based BRCA test will be similar to the BRACAnalysis test, except that it will look at those genes in FFPE tumor tissue, as opposed to germline DNA, and will use next-gen sequencing, rather than Sanger sequencing.

While germline mutations to the BRCA 1 and 2 genes are predictive for the risk of developing hereditary breast cancer, mutations to those genes in tumor tissue can help guide treatment for cancer patients, as they have been found to predict response to some drugs, such as PARP inhibitors and other DNA-damaging compounds.

Capone said that Myriad is "actively working with companies and investigators interested in this assay as a companion diagnostic for DNA-damaging agents."

Myriad did not disclose details on its other NGS-based tests or a timeline for when it would launch them.

Because the price of whole-genome sequencing has fallen dramatically, some have questioned the long-term viability of Myriad's BRACAnalysis test, which costs around $3,000 and sequences only the BRCA 1 and 2 genes. Already, Complete Genomics offers whole-genome sequencing for between $4,000 and $5,000, depending on the number of genomes ordered, and prices are predicted to continue to fall.

However, Capone said during the call that whole-genome and whole-exome sequencing are still not accurate enough for clinical purposes.

In the BRACAnalysis test, for instance, single-base accuracy must be 99.995 percent to ensure an accurate test result, he said. While next-gen sequencing can reach that level with deep enough sequencing, it is not cost-effective when looking at an entire genome or exome, he said.

Internally, the company tested whole-genome sequencing at 42-fold coverage and compared the BRCA 1 and 2 genes to the BRACAnalysis test. "There was significant variability, with some regions of the genes having insufficient coverage to ensure accuracy," Capone said. "We believe, based on this data and other in-house data, that accuracy would have to be improved by several orders of magnitude to meet the stringent requirements for clinical use."

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