Three-platform genetic sequencing offers hope for improved pediatric oncology diagnostics and precision medicine therapies

Dark Daily has long predicted that multiomics will someday play an important role in clinical laboratory diagnostic medicine. Now, new research from St. Jude Children’s Research Hospital provides early evidence of that prediction coming to fruition. 

Scientists at St. Jude’s have discovered that performing different genetic tests on pediatric cancer patients, and then combining those test results, may help guide and improve patient care.

The research was part of a St. Jude’s project called Genomes for Kids (G4K), a study to determine how genetic information may be used to diagnose and treat pediatric cancers.  Through this project, the researchers hope to learn why tumors form in children and predict how tumors will respond to certain treatments. 

‘It’s a Whole Lot of Sequencing.’

Few tragedies are worse than cancer in children. This is where precision medicine treatments can be critical, and multiomics may play an important role in the development of new therapies.

Multiomics refers to a biological analysis approach in which multiple “omes” are analyzed together in a collaborative way to locate relevant biomarkers and functional relationships. These “omes” include:

To perform their research, the St. Jude scientists examined 253 pediatric cancer patients by conducting whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing of their tumors. They also looked at the WGS and WES of non-cancerous tissues extracted from the same cancer patients.

“It is a whole lot of sequencing. I admit that,” Scott Newman, PhD, Group Lead, Bioinformatics Analysis at St. Jude’s, told The Scientist.

“With results available in a clinically relevant time frame, and pricing becoming increasingly comparable to the radiology and pathology tests, WGS is becoming more accessible to pediatric oncology patients,” said Scott Newman, PhD (above), Group Lead, Bioinformatics Analysis, at St. Jude’s, in an American Society of Human Genetics (ASHG) news release. (Photo copyright: ASHG.)

As a result of their three-platform testing, the researchers discovered there was at least one finding for each patient that could be useful in providing a diagnosis, revealing risks for individual patients, or pinpointing which drugs may be most beneficial for a particular patient in nearly 200 (79%) of the cases. Such findings are at the heart of precision medicine.

The researchers also compared their sequencing results to cancer panels that use next-generation sequencing (NGS) to target specific genes or mutations relevant to a certain cancer phenotype. During this portion of the research, they discovered that the cancer panels missed 11% to 16% of actionable genes relating to diagnosis, prognosis, and treatment. 

“This is either good news or bad news, depending on how you look at it,” Newman said. “Personally, I am amazed at how well these panels do and how well they have been designed. But, if you want to know every mutation that you would probably want to report, you have to do comprehensive sequencing.”

First Multi-Platform Genomic Sequencing Study

“To our knowledge, this is the first clinical study where this comprehensive three-platform genomic sequencing approach was offered prospectively to all pediatric oncology patients,” said Kim Nichols, MD, Director, Division of Cancer Predisposition at St. Jude’s, in a St. Jude’s blog post.  

The testing costs $8,600 per patient, but is considered worth it to improve patient diagnosis, prognosis, and treatment for pediatric cancer patients.

“Compared with the cost of many other procedures that children with cancer undergo, the cost is likely comparable, or even less—for example, compared with complex surgical procedures or multiple radiology tests,” Nichols said.

In addition, the test results are available in less than 30 days, which makes them more valuable, as time can be a critical asset to cancer management.  

The scientists hope this type of three-platform genetic testing can help guide care for pediatric cancer patients. 

Because so few of the molecular lesions in pediatric cancer are targetable by specific drugs, currently it is the diagnostic and prognostic insights provided by the three-platform approach that appear most clinically impactful,” said Nichols. “From a diagnostic perspective, tumors may look the same under a microscope, but the identification of specific genetic changes can direct you to the correct diagnosis, and therefore, the most appropriate therapy. From a prognostic perspective, you will have different risk stratifications depending on results.”

The results of the research were presented at the 2018 annual meeting of the American Society of Human Genetics in San Diego last October. The St. Jude’s researchers hope that this type of research can drive wider adoption of WGS in the assessment of pediatric tumors to improve patient outcomes. Pathologists and medical laboratory scientists will want to watch for additional research findings as the team at St. Jude’s uses this approach on more pediatric cancer patients.

—JP Schlingman

Related Information:

Genome, Exome, RNA Sequencing Applied to Pediatric Cancer Cases

Genome Sequencing Found Feasible and Informative for Pediatric Cancer Treatment

Recommendations Reported at ASHG 2018 Annual Meeting

Genomes for Kids Brochure

What You’re Missing If You’re Only Sequencing Exomes or RNA

Onco-Multi-OMICS Approach: A New Frontier in Cancer Research

Metabolomics Promises to Provide New Diagnostic Biomarkers, Assays for Personalized Medicine and Medical Laboratories

Might Proteomics Challenge the Cult of DNA-Centricity? Some Clinical Laboratory Diagnostic Developers See Opportunity in Protein-Centered Diagnostics

Introducing “Salivaomics” As the Basis for Cheap, Accurate Diagnostic Tests—Administered by Your Dentist!