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Baylor, Texas Children's Hospital Aim to Make Sequencing Routine with New Pediatric Center

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By Molika Ashford

Baylor College of Medicine's Human Genome Sequencing Center and the Texas Children's Cancer Center have joined to create the Pediatric Center for Personal Cancer Genomics and Therapeutics, with the goal of routinely sequencing all new patients at the TCCC.

The partners have begun several projects targeting particular cancers and plan to work over the next year on expanding the new center's purview, William Parsons, the director of the center and pediatric oncologist at TCCC, told Clinical Sequencing News.

In collaboration with other regional groups, the center plans, eventually, to sequence all new pediatric cancer cases in the state of Texas — approximately 1,000 a year. The hope is that their approach will lead to new and improved therapies and the development of diagnostic tests.

"We have a first-rate and very large clinical hospital at Texas Children's such that … in terms of access to samples … there are very good opportunities for that," Parsons said. "And on the downstream end, if we make a genomic discovery … we have the clinical facility and research capabilities to investigate what we found."

"For me, the selling point was the opportunities of those two things, and the ability to put them together. So that's what we've been trying to do," he said.

Richard Gibbs, director of Baylor's Human Genome Sequencing Center, told Clinical Sequencing News that a variety of sequencing platforms will be used in the new pediatric project. "It's simply a fact that the largest capacity is coming from the Illumina HiSeqs right now," he said. "But we also need replication on other platforms and validation. We'll be exploring other platforms for their potential to give different views of the data."

The partners initially plan to focus on exome sequencing, said Parsons, "mainly because the cost is significantly less. But [also] in terms of the information we can gather that is potentially actionable and interpretable, we're still way behind in terms of interpreting what non-coding changes might mean. So in terms of practically doing something with it, I think exomes are still the way to go."

Gibbs said that the center also plans on "balancing [exome sequencing] with a reasonable number of whole genomes" to "cover all the bases."

Currently the partners are working on building the infrastructure to expand from smaller sequencing studies of specific childhood cancers to a system for routinely sequencing every new pediatric patient that comes into the Texas Children's Cancer Center.

There are a handful of relatively common tumor types in children, along with a "huge variety" of rare tumors, Parsons said, many of which are never going to be the top target of a specific sequencing project. Taking a more agnostic approach will allow the group to gather data on the rare tumors "in a way that if we didn’t systematically do things, we might not."

"That's actually one of the interesting parts for me," said Parsons, "because these are also the patients we don't really know what to do with in terms of what treatments to give, so any knowledge we get even on small numbers would be pretty important."

Once the center is sequencing all new patients, Parsons said it hopes to expand even further — collaborating with other academic centers in Texas to try to sequence all new pediatric cancers in the state.

Secondly, the group is working on connecting with tumor biology and functional genomics researchers within the Baylor community. "We are trying to focus [these researchers] on taking advantage of the data that's coming out of these [sequencing studies]; trying to make it clear that this data is available to investigators studying the biology of specific tumors, and trying to set up the infrastructure and plans to routinely encourage that," Parsons said.

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In a third aspect of the project, the center plans to focus on working out the kinks involved in applying the results of its sequencing work to clinical practice. "The future is clearly going to be that this is something that's routinely done, but making it happen in a time frame that is sufficient to allow the data to be used for each patient in a clinically reasonable way is another challenge," said Parsons.

According to Gibbs, the center is embarking with a "research discovery mode" in mind but will try to move into a "robust clinically effective mode," as soon as possible.

While he didn't have specific examples of how the group is working on this issue, Gibbs said work on rare inherited diseases, which he called a "more simple problem," might inform researchers moving forward in the investigation of pediatric cancer. Recently, Gibbs and colleagues published a paper in Science Translational Medicine describing how sequencing the genomes of the teenage twins of Life Technologies CIO Joe Beery led them to an unexpected treatment possibility that helped improve the symptoms of the children's disease (CSN 6/15/2011).

Right now, Parsons said, the new center is "at the stage where we're all working together on a number of projects … and we have both external and internal funding to support what we want to do."

The center has already begun collaborating on several pediatric sequencing studies targeting particular cancers. "We're working on a variety of brain tumors and solid tumors," he said. "Specifically, we're funded to do a big study of hepatoblastoma, which is the most common malignant liver cancer in kids." Other focuses include malignant brain cancers, Parsons said.

Some funding has come from the Cancer Prevention Research Institute of Texas, including approximately $3 million toward hepatoblastoma work, Parsons said, as well as additional money for the sequencing center's work in general.

"We've proven, and others have proven, we can do these sorts of sequencing studies. So now we have to prove that we can expand it, prove that we can routinely do it, and hopefully along with that, we can tie in epidemiologic data, clinical data, and really be able to ask a lot of really interesting questions," Parsons said.

Gibbs added that he hoped a deep investigation of pediatric cancer might also shed light on adult disease. "I just think … there's a bit of an analogy here … where some of the very common diseases in adults are very hard to solve, but the simple straightforward diseases … that occur in children are sometimes more tractable, more possible to solve."

"Some aspect of this is involved in this program. The pediatric cancers may be likely to give us insights into all cancers," he said.


Have topics you'd like to see covered in Clinical Sequencing News? Contact the editor at mashford [at] genomeweb [.] com.

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