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Gustave Roussy, IntegraGen Partner to Support Clinical Cancer Trials with Exome, RNA Sequencing


NEW YORK (GenomeWeb) − In an effort to support clinical trials with cancer exome and transcriptome sequencing, cancer center Gustave Roussy and genomics firm IntegraGen, both of France, said last month that they are jointly establishing a new high-throughput sequencing laboratory.

The sequencing unit, which is expected to be up and running by midyear, will be housed at Gustave Roussy, based in Villejuif, a suburb of Paris, and operated by IntegraGen, located in Evry just south of Paris.

IntegraGen has already been providing genomic services to Gustave Roussy for the past five years or so, and was able to set up a sequencing lab more quickly than the institute would have been able to on its own, according to Eric Solary, director of Gustave Roussy's Integrated Research Cancer Institute in Villejuif (IRCIV).

The new facility helps to expand an existing personalized medicine program at Gustave Roussy that started in 2010. Using targeted sequencing of two candidate genes and comparative genomic hybridization arrays, researchers at Gustave Roussy and their collaborators directed the treatment of metastatic breast cancer patients, a study they published earlier this year in Lancet Oncology. In the meantime, they have increased the number of sequenced actionable genes to about 50, Solary said, but "we wanted to do more."

The new laboratory, which will be located in Gustave Roussy's Molecular Medicine building, close to an existing sequencing facility, will be "essentially technology agnostic" but equipped initially with Illumina's new NextSeq 500 platform, according to IntegraGen CEO Bernard Courtieu.

The goal of the lab is to provide exome and transcriptome sequencing data from patient samples – mostly biopsies of metastases – for clinical research, in particular as part of prospective clinical trials to test new drugs and concepts of personalized medicine. More than 10 such trials for different types of metastatic cancers are currently ongoing at Gustave Roussy, and the aim is to sequence samples from 150 patients during the first year.

"The results will be used to treat patients in the setting of the clinical trial," Solary said, helping to choose the most appropriate targeted drugs. The focus will be on mutations in actionable genes, which will initially be validated by an orthogonal method.

Information about mutations in the remainder of the exome, as well as the transcriptome, may come in handy later, he said, for example to help understand patients' response or resistance to a particular treatment.

While most of the patients will come from Gustave Roussy, which treats about 47,000 cancer patients per year, the facility will also be accessible to other hospitals, and is open to collaborations with outside research teams for other types of trials.

Going forward, the lab will also seek to become CLIA-certified, allowing the researchers to collaborate on similar trials with groups in the United States.

One of the challenges is to obtain biopsies of sufficient quality and quantity, Solary said, and institute researchers have optimized methods for obtaining material suitable for sequencing.

IntegraGen will sequence the exomes of tumor/normal pairs at 120x coverage, as well as the transcriptome, within 16 days of their biopsy, which Solary said is "a good timeframe for clinical use."

IntegraGen will provide the first bioinformatic analysis of the data, which clinicians at Gustave Roussy will interpret clinically, though details of the workflow still need to be finalized.

Initially, clinicians will not report back any incidental findings of disease-predisposing mutations. Best practices for returning such findings are still under discussion by ethics panels in France, Solary said, and the researchers plan to adhere to any recommendations once they become available.

The new sequencing facility helps implement a new, €1.5 billion ($2 billion) plan to fight cancer that French president, François Hollande, announced in February. One of the objectives of the five-year plan is to increase the use of cancer exomes in clinical research, and "this platform is one of the very first, if not the first, being able to deliver what's required by this plan," Courtieu said.

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