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ddn Cancer Research Portal Exclusive: Tackling cancer one genome at a time
MEMPHIS, Tenn.—Some partnerships can lose their momentum as time goes on, but for the St. Jude Children's Research Hospital – Washington University Pediatric Cancer Genome Project (PCGP), that particular problem is nowhere in sight. Four months into its second year, the initiative has already released four sets of findings, with more to come.
The initiative began in January 2010. St. Jude is the first and only National Cancer Institute-designated Comprehensive Cancer Center that is focused solely on children, and has more than 50 years of experience as well as an extensive library of tissue samples and data. Washington University School of Medicine in St. Louis is a leading genome sequencing center and participated in the mapping of the human genome. The project is slated to run three years, a $65 million undertaking that will sequence and study the cancer genomes of more than 600 children. At the time of the PCGP's origin, a complete pediatric cancer genome had yet to be sequenced.
Washington University has received normal and cancerous tissue samples from 600 patients from St. Jude's, whose repository houses more than 50,000 samples. The project is focusing on the most common and most aggressive pediatric cancers, including brain, blood, bone and other cancers. The data gathered throughout the project began to be reported through peer-reviewed channels this year, in addition to being made available through the project's Explore website, which offers details on the project's progress as well as additional information on the data gathered so far.
Pediatric cancers remain the leading cause of death by disease in children over the age of one, and recent studies have found that while childhood cancers can appear in the same organs and locations as adult cancers and share some similarities, they usually have several significant biological differences.
Dr. Suzanne Baker, corresponding author of the study of one of the PCGP's recent studies, says she believes the project's focus on pediatric cancers as being different from adult cancers is important. Baker is a member of St. Jude's Department of Developmental Neurobiology and co-leader of the St. Jude Neurobiology and Brain Tumor Program.
"Pediatric cancers are different from adult cancers in a number of different ways. Although they're much less common than the most common adult cancers, they are often very selectively seen just in children. And so that suggests that maybe the mutations that drive those tumors in children would be different from the ones that are driving cancer in adults," says Baker. "And so the Pediatric Cancer Genome Project is very important in the sense that if we didn't take an unbiased look and just try to look at all of the genes across the entire genome and try to identify the mutations that are frequent in childhood cancer, we might not find those mutations if we were just looking for things that had already been identified in adult diseases."
The year has been a busy and productive one for the PCGP so far. In January, the project announced a trio of findings, including identifying a new gene target for treating the childhood eye tumor retinoblastoma. Researchers also announced the discovery of a potential approach for treating a subtype of acute lymphoblastic leukemia (ALL) known as early T-cell precursor ALL. On January 29, the PCGP released findings that a genetic mutation had been tied to diffuse intrinsic pontine glioma tumors, which comprise 10 to 15 percent of brain and central nervous system tumors in children. (See 'Kids on the brain' for the full story.) Most recently, the project discovered the first gene mutation associated with a form of neuroblastoma that affects adolescents and young adults, an alteration that offers a clue about the genetic basis of the connection between age at diagnosis and treatment outcome. That latest discovery was published in the March 14 edition of the Journal of the American Medical Association.
According to Baker, there are a variety of cancer types on the docket to be analyzed, including neuroblastoma, medulloblastoma, several subtypes of leukemia and a number of solid tumors.
"I do think because the childhood tumors are less common and therefore less intensely studied in general, that there may be more unexpected or novel findings coming out of specifically looking at childhood cancers," says Baker.
Four months into the project's second year, 265 patients' genomes have been sequenced and analyzed, with 16 of those having been published, according to the PCGP's Explore website. Sequencing is currently underway for 35 more cancerous and regular genomes, with 300 more waiting in the pipeline.