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Wash U, St. Jude Will Sequence 600 Pediatric Cancer Genomes on Illumina's GA and HiSeq

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By Monica Heger

Washington University and St. Jude Children's Research Hospital announced this week a project to sequence the genomes of more than 600 samples of childhood cancers using Illumina's Genome Analyzer as well as the HiSeq 2000.

The project is already underway: Five samples are currently being sequenced and scientists completed the first sample, an infant childhood leukemia, this week on the GA, Elaine Mardis, co-director of the Genome Center at Washington University in St. Louis, told In Sequence.

The project will span three years, and the researchers will sequence the genomes of both cancer and normal tissues from the same child. Cancer types will include leukemia, soft tissue cancer, and brain cancer, and the samples have already been collected at St. Jude's Hospital.

Kay Jewelers is contributing $20 million to the $65 million project, and St. Jude's Hospital is funding the remainder of the project, with in-kind contributions from Washington University.

Mardis said that 10 Illumina GA sequencers are currently being used for the project. The original proposal called for the purchase of up to 10 more GAs in the second year of the project, but now the genome center is planning to buy Illumina's newly launched HiSeq 2000 instruments instead, and will determine the exact number at a later date.

Scientists will sequence the genomes of both cancer and normal tissues from the same patient to about 30-fold coverage, using a paired-end approach with read lengths of around 100 base pairs.

While the Washington University scientists will focus on whole-genome sequencing of the samples, scientists at St. Jude's will contribute additional analyses like RNA-sequencing and characterizing methylation and epigenetic changes, also on the Illumina GA, said Mardis.

The patient samples will come from St. Jude's Hospital, which has a repository of over 50,000 samples with detailed clinical annotation, including "information about the child, how they were treated, what the outcomes were, and a lot of extensive molecular characterization from many of these samples," said Mardis. "So we'll be able to leapfrog directly from sequencing into heavy analysis in order to understand the disease at the most exquisite level of detail."

Washington University is also involved in a separate, multi-institutional cancer sequencing project, the Cancer Genome Atlas, which is jointly funded by the National Human Genome Research Institute and the National Cancer Institute. Mardis said that this project is similar in that it involves whole-genome sequencing of cancer samples, but the main difference is that the current project will focus solely on childhood cancers, with the goal of uncovering the origins and causes for better prediction and to find new targets for treatment.

In addition, a previously internal cancer genome sequencing project focusing on acute myeloid leukemia has now been added to the Cancer Genome Atlas, according to a Washington University spokesperson. Over the last two years, the Wash U genome center has published analyses of two AML genomes sequenced using the Genome Analyzer, among the first of such whole-genome cancer studies. The researchers are currently in the process of sequencing 50 AML genomes by the spring of this year, she said.

The advances that have been made over the last 45 years in treating childhood cancers have been incremental, said St. Jude's Director and CEO William Evans in a webcast this week. "And, they have come from finding optimal ways to use anti-cancer drugs that were developed for adult tumors, not children."

Focusing on pediatric cancers will enable the development of treatments specifically for children that are "more effective and less toxic," he said.

The Wash U – St. Jude's project is not the only cancer genome project to focus on childhood cancers. Last month, a consortium of researchers in Germany said they were going to sequence 300 tumor samples and matched controls of each of two childhood brain tumor types under the umbrella of the International Cancer Genome Project (see In Sequence 12/15/2010). That five-year project is funded with €15 million ($22 million) from the German government.

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