A study led by St. Jude Children’s Research Hospital shows that a combination of whole-genome, whole-exome and RNA sequencing can improve many aspects of diagnosis and treatment for children with cancer, ultimately leading to better prognosis and outcome for these patients.
The team found that 86% of the children with cancer who participated in the study had cancer-related variants in either germline or tumor DNA. These variants were linked to cancer predisposition, diagnosis, prognosis prediction or how effective a therapy would be.
Notably, the researchers estimated that 1 in 5 of these patients had relevant mutations that would not have been detected without using the three-pronged approach.
“Some of the most clinically relevant findings were only possible because the study combined whole genome sequencing with whole exome and RNA sequencing,” said Jinghui Zhang St. Jude Department of Computational Biology chair and co-corresponding author of the study, which is published in Cancer Discovery.
Overall, 309 children with newly diagnosed (85%) or relapsed cancer (15%) were included in the Genomes for Kids study. Of these, 253 had their tumors examined using all three sequencing methods and 300 also had germline testing. Of the included children, 41% had blood cancer, 31% brain tumors and 27% non-neurological solid tumors of different types.
Overall, the combined sequencing picked up variants that aided diagnosis in 53% of the children, gave an insight into cancer prognosis in 57%, and detected cancer predisposition in 18% of the children.
In addition, 25% of those tested had variants that could impact therapeutic choices and help to decide on the most effective treatment for those individuals.
“Therapy was changed for 12 patients based on tumor genomic data, with one patient moving on to curative allogeneic stem cell transplantation, and four patients exhibiting prolonged disease stabilization,” write the authors.
The use of whole genome sequencing allowed the team to pick up some hard to detect cancer-related mutations such as activating gene fusions, enhancer attacks and small intragenic deletions in 36%, 8% and 15% of tumors, respectively.
“We want to change the thinking in the field,” said David Wheeler, St. Jude Precision Genomics team director and a co-author of the study. “This study showed the feasibility of identifying tumor vulnerabilities and learning to exploit them to improve patient care.”
This kind of three-way sequencing approach is not widely available at the moment, mostly due to the resources and time it requires, but the authors are hopeful that this may change in the near future.
“As genomic sequencing technologies become less expensive and more widely available, their use will be an important adjunct to gene panels in the evaluation and management of children with newly diagnosed as well as relapsed or refractory cancers.”
The Genomes for Kids study helped to launch the St. Jude’s clinical genomics program, which has now enrolled around 2700 cancer patients. The research team have made the data from this study freely available to researchers working in this area to help speed up research into childhood cancers.
