As several European diagnostics labs have ported BRCA1 and BRCA2 testing to next-generation sequencing, Myriad Genetics has not yet found a platform that satisfies its needs for BRACAnalysis, its most important test today.
"We are continuously looking [at new technologies] to potentially upgrade our platform, when the technology gets to a point where it is cost-effective, has high enough accuracy, and can provide a turnaround time that is within our standards," a company spokesperson told Clinical Sequencing News.
Myriad's BRACAnalysis currently uses Sanger sequencing in combination with PCR, quantitative PCR, or array comparative genomic hybridization to detect rearrangements. The turnaround time for results is less than two weeks.
Over the last 10 years or so, the company has upgraded its platform four times, moving to updated capillary electrophoresis systems, and is currently using Life Technologies' Applied Biosystems 3730 DNA Analyzer, the spokesperson said.
Myriad currently has several 454 instruments as well as Illumina HiSeqs and MiSeqs in its research and development facility "and we have looked at the new Ion Torrent technology quite extensively as well," she said.
While she did not specify the accuracy, cost, and turnaround time metrics a new platform would need to fulfill, she said that none of today's platforms will suffice. "Potentially, the HiSeq 2500 could satisfy these requirements," she added.
The 454 platform, for example, has accuracy issues with homopolymers, which is a problem because the BRCA genes have more than 50 homopolymer regions, she said.
Gary King, Myriad's executive vice president of international operations, told CSN that the company has optimized all the steps of its Sanger-based platform, which analyzes about 1,000 samples a day, including primers, chemistry, automation, and bioinformatics (see Q&A, this issue).
He said that the firm is "constantly approached by instrument providers to check out their new instruments," but so far, it has "found nothing that's as accurate, as fast, and as reliable as Sanger sequencing."
However, Myriad is exploring next-generation sequencing for other kinds of tests. Last December, the company said it is developing an NGS-based BRCA test that will analyze formalin-fixed paraffin-embedded tumor tissue, a hereditary cancer test, a colon cancer diagnostic test, and an early cancer detection test (CSN 1/4/2012).
In the meantime, several laboratories in Europe are betting on next-gen sequencing for BRCA testing. The Leeds Clinical Molecular Genetics Laboratory in the UK, for example, has tested more than 1,200 patients for mutations in the BRCA genes using the Illumina GAIIx platform (CSN 7/11/2012). The test has a turnaround time of 28 working days.
Also, UK-based NewGene has been providing BRCA1 and 2 testing on the Roche 454 GS FLX in combination with multiplex ligation dependent probe amplification to detect insertions and deletions (IS 8/4/2009), offering a standard turnaround of six weeks, and a fast turnaround time of four weeks.
Sistemas Genómicos of Spain has also been offering BRCA testing on the 454, using the GS Junior.
In the meantime, Multiplicom, a Belgium company, is about to launch a CE/IVD-marked multiplex PCR amplification kit for BRCA next-gen sequencing (CSN 7/3/2012).