Under a five-year, $10 million grant from Hyundai Motor America, researchers at Children's Hospital of Orange County in collaboration with the Translational Genomics Institute are sequencing and interpreting genomes and transcriptomes from recurrent and refractory pediatric and young adult cancer cases, with the goal of delivering data to primary oncologists in clinically relevant turnaround times.
The group is employing both Complete Genomics' service and Illumina's newly launched RapidTrack service for whole-genome sequencing. In addition, the Scripps Research Institute is doing the RNA-seq.
Illumina's RapidTrack sequencing service, launched in June, is being offered through its CLIA lab and is based on the HiSeq 2500. Recently, beta-testers at TGen said they plan to use the service for rare disease sequencing (CSN 7/25/2012).
So far, about 13 patients have had their genomes and transcriptomes sequenced under the CHOC project and the team is now in the process of analyzing the results. Of these, 10 patients have had their genomes sequenced by Complete and three have been sequenced by Illumina.
Leonard Sender, the medical director of Hyundai Cancer Institute at CHOC and principal investigator of the study, told Clinical Sequencing News that sequencing is done to very high coverage — 90x for the tumor genome and 30x for the normal.
Using the RapidTrack service has reduced sequencing turnaround time from around two months with Complete Genomics to two weeks. Analysis by the hospital's molecular profiling tumor board adds an additional two weeks, he said.
Sender said that the team will continue to use both Complete and Illumina, depending on the case. In some cases there is a standard treatment available and turnaround time is less critical, but in other cases, such as with rare tumors, it's important to have the sequence information as soon as possible, he said.
"I believe the future of oncology is based on a deep understanding of the whole-genome sequence" of a patient's tumor, Sender said. It's important to do this on an individual basis, he added, because "just from our preliminary data, these tumors don't always have the mutations you see published in the literature." Those are often based on aggregate data, he said, but cancer is heterogeneous and can vary dramatically person to person.
Additionally, he said, in one case he's found a translocation that actually changes the diagnosis of the cancer. This is important, he said, because "when you look at a tumor and think it's tumor X, you go down a path of treatment," but if that initial diagnosis is wrong, the chances are greater that the treatment will be ineffective — which is a huge burden both financially and psychologically.
The study is open to anyone under the age of 21 who has recurrent or refractory cancer of any type, Sender said. The project is focusing on these cancers because while 80 percent of pediatric cancers are cured, the cancers that recur are almost always fatal, he said.
The study will seek to evaluate whether whole-genome sequencing can provide actionable data in clinically relevant timeframes, as well as study the psychosocial and ethical issues associated with the use of genomic data in cancer treatment, said Sender.
In reality, "the chance of finding something new is small," he acknowledged. For example, there may be no drugs available that target the mutations or, if they are available, they may not be approved for that indication or may be unaffordable, he said.
This possibility is stated very clearly in the informed consent forms for the project, as well as in discussions with parents of participants, said Sender.
Parents have to go through two different informed consent processes — the first to give the researchers access to tissue and blood samples, and the second to allow the data to be analyzed by the tumor board and returned to the treating oncologist.
Sender said that the goal is to have between 50 and 100 children sequenced and analyzed by this time next year, and to continue to expand the program as funding allows.
Additionally, he hopes to use sequencing to study cancer evolution in patients and sequence tumors at diagnosis, relapse, and progression.
"The goal is to prove that there's a role for this type of technology, which will hopefully lead to improvement of patient care," he said.