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Canada Undertakes Cancer Sequencing Study For Hard-to-Treat Pediatric, Young Adult Cases

CHICAGO (GenomeWeb) – Investigators at dozens of centers across Canada are teaming up to offer genomic profiling to children and young adults with relapsed or treatment-refractory cancer across the country.

The prospective study — known as "Precision Oncology for Young People," (PROFYLE) — is supported by C$16.4 million (US$13.1 million) as of February, including C$5 million in seed funding from the Terry Fox Research Institute.

Hospital for Sick Children (SickKids) researcher Adam Shlien provided information on the clinical cancer sequencing program at the American Association for Cancer Research annual meeting here yesterday. He also touched on early results from a similar research study at SickKicks called "Kids Cancer Sequencing Program" (KiCS).

KiCS provided an opportunity to start evaluating the infrastructure, pipelines, and analytical approaches that will be needed as genome sequencing becomes a routine part of oncology, explained Shlein, who co-led the project with SickKids researcher and PROFYLE project leader David Malkin. Corresponding germline samples are being sequenced to identify hereditary cancer risk variants that may be relevant to pediatric cases at hand, as well as other family members.

For that study, researchers have been using Illumina HiSeq 2500 and NextSeq 500 instruments to do deep sequencing on coding sequences for roughly 800 cancer-related genes in matched tumor and normal samples from each individual. They are also doing shallow, whole-genome sequencing with Illumina HiSeq X Ten instruments, he said, along with RNA sequencing.

Starting with DNA sequences from a group of highly mutated tumors profiled for KiCS, for example, Shlein and his colleagues embarked on an investigation that brought in additional retrospective data, RNA sequences, and clinical outcome cues to find — and start characterizing — a potentially clinically informative subset of Ewing sarcomas.

In addition to carrying a specific type of complex rearrangement with apparent ties to aggressiveness, transcriptome shifts, and other features, such tumors are offering insights into the evolution of primary and relapsed tumors.

The Canada-wide PROFYLE effort is expected to continue building on KiCS and similar programs in Vancouver and Montreal, Shlein said. It will span at least 20 participating institutions and investigators are aiming to enroll any child or young adult under the age of 30 who have relapse, refractory, or otherwise difficult-to-treat tumors.

For an initial PROFYLE cohort, the team has sequenced samples for 143 patients, including 184 tumor samples. Tumor samples taken at two time points are available for one-quarter of the cases, Shlein said, and more than half of the tumors were collected post-therapy.

Around 56 percent of the tumors sequenced so far contained clinically informative alterations, he noted — from variants that may be targetable for treatment to those expected to offer insights into cancer diagnoses or prognosis.

"[I]nstead of working in somewhat independent silos, we have created a massive formulized collaborative and co-operative program to achieve this goal," Malkin said in a statement when SickKids announced the project in February.

"The second, longer-term hope is that we will have developed a mechanism as we learn more and more about genetics and genomics of cancer, so that every newly diagnosed child, adolescent, and young adult will eventually have the genome of their tumour sequenced, to give them more opportunities for therapy and accelerate their return to health," he added.

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