A new program launched by the Institute of Cancer Research in the UK and the Royal Marsden NHS Foundation Trust, a London-based cancer center, aims to bring cancer predisposition gene testing to all cancer patients in the UK.
Funded with £2.7 million ($4.1 million) from the Wellcome Trust, the three-year program, called Mainstreaming Cancer Genetics, will use a 97-gene panel developed in collaboration with Illumina and will start offering diagnostic testing for subsets of genes next year. Illumina commercialized the panel as a research-use-only capture product called TruSight Cancer last year (CSN 9/12/2013). ICR scientists are also working with scientists at the Wellcome Trust Centre for Human Genetics at the University of Oxford, who are developing data analysis methods for the test.
According to Clare Turnbull, head of ICR's predisposition and translational genetics team and one of the leaders of the program, the goal is to provide cancer predisposition testing to a larger number of cancer patients and their families by "lowering the thresholds by which we offer genetic tests."
One way to achieve this is to offer cancer patients the test through their oncologists as part of their routine appointments, rather than via referral to a clinical geneticist as is currently done. "The change will be the setting in which they're having their genetic testing," she said.
The 97 genes on the panel confer a "significant risk" for cancer and were selected for "clinical utility and management implications," she said. Ninety-four of the genes are sequenced in full, while the remaining are analyzed in part. In addition, the panel includes common cancer predisposition SNPs from genome-wide association studies, she said.
For more than half the genes on the panel, no genetic tests exist in the UK today because mutations in those genes are rare, so "it's really not worth the while of any lab to develop these tests in isolation," Turnbull explained. In a large multi-gene panel, those genes can be included without significantly increasing the test's complexity.
Clinical testing will start sometime next year and will be performed in ICR's translational genetics laboratory, an existing diagnostic lab, using the Illumina HiSeq 2500. The instrument can be run in slow mode with higher throughput, which takes about 11 days, or in fast mode with lower throughput, which takes 27 hours. "In terms of turnaround time, the slow mode is entirely acceptable," Turnbull said, but if samples fail and need to be repeated, or if a treatment decision is contingent on the test result, the lab may opt for the fast mode.
At the moment, the lab is testing how many samples it can multiplex in one run while maintaining the sequence quality and coverage necessary for a diagnostic-grade test. It is also validating the panel with a number of positive controls and continues to improve it, having recently added genes and changed the probe density and layout.
Initially, testing will only be available for certain types of cancer – starting with breast and ovarian – and will report on a subset of genes from the panel, in the first instance the BRCA1 and BRCA2 genes. "We will be running the full panel technically and reporting on parts of it as appropriate as we roll out," Turnbull said.
Next, testing will be expanded to larger numbers of genes and more cancer types, she said, until the full panel is eventually offered. "There are a number of structures that need to be explored and developed in terms of the consent and clinical processes for testing a patient for 97 genes," she said.
The cost for the full panel will be "a few hundred pounds," which she said is low, given that a number of single-gene tests offered through the UK's National Health Service currently cost more than £1,000 ($1,512).
The results go back to the oncologist who ordered the test and are expected to be negative in about 90 percent of cases. If the result is positive, the patient is referred to a clinical geneticist. The ICR is currently developing materials for communicating cancer risk to mutation carriers, but "we still envisage these being managed by specialists and experts in management of genetic conditions," rather than oncologists, Turnbull said.
It is unclear whether the Mainstreaming Cancer Genetics program will be the first effort to implement Illumina's TruSight Cancer panel in the clinic. According to Matt Posard, senior vice president and general manager of Illumina's translational and consumer genomics business, interest in Illumina's TruSight content sets "has been tremendous" and "multiple institutions" are evaluating them. Among them is Kindstar Global in China, which is using TruSight assays – including the cancer panel – as part of a strategic collaboration with Illumina to validate and implement molecular assays in its laboratories. The collaboration, he said, allows Kindstar "to expand its esoteric and specialty testing services offerings within its network of more than 3,300 hospitals across China."
However, Illumina isn't the only firm that has developed or is developing a panel for cancer predisposition testing. GeneDx, for example, is developing its own hereditary cancer panel. "We use our expertise to choose the most important clinically relevant genes for our tests, where the results will be meaningful in the care of the patients," said Sherri Bale, the firm's managing director. GeneDx will fully sequence all the genes on its panel, "thus providing higher sensitivity in a clinical setting," she added.
Myriad Genetics is also developing a multi-gene hereditary cancer panel, called MyRisk Hereditary Cancer, which will initially include 25 genes. The company said recently that it holds IP rights to several genes on its panel, which could potentially prevent competitors from including these in their products (CSN 5/15/2013). GeneDx, Illumina, and ICR all declined to comment on Myriad's patents, and how they might affect their tests. "Their IP position is not known to us at the moment," Turnbull said.