TGen Sequencing Study Tracks Mutations in Childhood Cancer Progression

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Findings from a 10-year study led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that deeper genomic analysis and therapies that rely on the body’s immune system are the way forward in this field. help out. The study was published today in Cancer Research, a journal of the American Association for Cancer Research

Researchers used genomic sequencing to analyze 250 solid tumors from 202 young patients enrolled in the Beat Childhood Cancer Research Consortium’s clinical trials at more than 40 U.S. hospitals and universities.

Their study focused on those children and young adults whose cancers were refractory or recurrent. Researchers found that such tumors had a higher number of genetic mutations than at the original diagnosis. More than two in five tumors mutated after chemotherapy.

Jeffrey Trent, Ph.D., TGen president and research director, and one of the study’s senior authors, noted that many of the childhood cancers showed different mechanisms of immune evasion and generally did not show infiltration by immune cells. This finding could potentially open the door for additional research that could identify and develop new therapeutic options.

“Between the potential for targeted therapies and new ways to use the immune system against cancer, we are encouraged by the potential to use the information from our research to help these children, give them and their families answers and hope for the future.” said Trent.

Cancer is the leading cause of disease-related death in children in the country. Although survival rates for children with cancer are improving, not all children respond to current medical treatments.

“Sometimes, despite the best medical care and significant advances made in cancer treatment in recent years, tumors come back,” said Sara Byron, PhD, associate professor in TGen’s Integrated Cancer Genomics Division, and one of the lead authors of the research. “Relapses probably occur because the first treatments fail to eliminate some of the original cancer cells. We need to know why this is happening and find ways to treat these tumors more effectively.”

The study’s other senior author, Giselle Saulnier Scholler, MD, agreed, adding that most patients in this study had tumors expressing multiple neoantigens, which are proteins on the surface of tumor cells that serve as therapeutic targets. can be used. More than half of the patients in the study expressed five or more neo-antigens.

“This research highlights the importance of genomic sequencing for pediatric cancers at any progression as we gain insights into how tumors mutate over time and mechanisms of resistance, which could have important clinical implications,” said Sholler, director of the Isabella Santos Foundation. Solid and Rare Tumor Program at Atrium Health Levine Children’s, where she is a professor of pediatric oncology. Sholler is president of the Beat Childhood Cancer Research Consortium.

Will Hendricks PhD, an assistant professor in TGen’s Integrated Cancer Genomics Division, and another of the study’s lead authors, said this study — with its high demand for computing speed and computing power — was only possible because of a multi-institutional effort. and critical support from Dell Technologies.

“This groundbreaking study provides unique insights gained from in-depth genomic analysis of some of the most clinically challenging tumor types in children,” Hendricks said.

By partnering with Dell Technologies, TGen has reduced the computation time for these tumor analyzes from weeks to hours. This was instrumental in providing timely results for the patients and their oncologists. The power of applying the latest technologies to help decipher the complexity of the human genome continues to drive better treatments for patients.

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