RNA Sequencing May Be Able to Help Target Therapies for Pediatric Cancers

Genomic profiling of tumors has become standard in oncology, but tumors in children often do not have actionable DNA aberrations, requiring another way to effectively target treatment for these patients. A study in JAMA Network Open found that RNA sequencing from pediatric and young adult patients may be a feasible approach.

“In pediatric cancer, it often isn’t a DNA mutation driving the cancer but an error in development caused by a change in how gene expression is regulated,” Olena Vaske, PhD, BSc, the Colligan Presidential Chair in Pediatric Genomics at the University of California, Santa Cruz (UCSC), explained in a statement.

Vaske and colleagues looked at 144 tumor samples from 128 patients with pediatric cancer. The patients were enrolled in 4 precision medicine clinical trials in the United States and Canada. The patients underwent tumor RNA sequencing.

The participating institutions sent the UCSC researchers the RNA sequencing data. Each site had its own precision medicine protocol and UCSC served as a third party conducting secondary analysis of the tumor data from each site.

“This was designed as a feasibility study to show that we can do this—get the data for prospective patients and process and analyze it fast enough to be useful,” said Vaske. “We showed for the first time that this framework can be used consistently across separate precision medicine clinical trials.”

They found that 99 of the RNA sequenced data sets had an outlier gene expression of 1 of 92 actionable genes. FLT3 was the most common gene expression outlier and was overexpressed in 16 samples in hematopoietic tumors. BTK in hematopoietic tumors and CDK6 in both hematopoietic and nonhematopoietic tumors were both overexpressed in 14 samples each. PTCH1 was the most common gene expression outlier in nonhematopoietic tumors (11 samples).

In comparison, DNA mutation information was only potentially useful in 46% of the samples studied.

The next step is to directly evaluate the clinical utility of this approach, Vaske explained.

“Our work suggests that direct investigations of the clinical utility and effectiveness of tumor [RNA sequencing]—derived gene expression information will be valuable, and the next phase of our project will focus on defining the incremental benefit of this approach,” the authors wrote.

Reference

Vaske OM, Bjork I, Salama SR, et al. Comparative tumor RNA sequencing analysis for difficult-to-treat pediatric and young adult patients with cancer. JAMA Netw Open. 2019;2(10):e1913968. doi: 10.1001/jamanetworkopen.2019.13968.