NGS Clinically Useful for Pediatric Cancers
From - Diagnostic Testing & Emerging Technologies The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center released data on its first… . . . read more
The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center released data on its first 100 patients, which shows that integrating clinical next-generation sequencing (NGS) into pediatric hematology-oncology practice is feasible and has “broad” clinical utility. According to the study published Dec. 23, 2016 in Genome Medicine, genomically informed data impacts diagnosis and prognosis, as well as treatment and other significant health maintenance decisions.
The PIPseq program was initiated in 2014 to prospectively integrate NGS into clinical decision making for high-risk pediatric cancer patients. (High-risk patients had a prognosis of less than 50 percent five-year survival, rare cancer without standard of care therapy, suspected cancer predisposition, or relapsed disease). High-risk patients account for about one-third of the total clinical practice.
The first 101 consecutive participants (mean age, 9.3 years) had a total of 120 samples sequenced between January 2014 and April 2016. Results were initially reviewed by a molecular pathologist and then by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient’s electronic medical record. Testing included full cancer whole exome sequencing (cWES ; tumor, germline, and RNA; n = 63); cWES without RNA (n = 19); RNA only (n = 3); targeted tumor panel sequencing (Columbia Comprehensive Cancer Panel of 467 cancer-associated genes; n = 13); and constitutional WES (proband and parental blood; n = 22).
“While we used a variety of analytical approaches matched to the clinical indications, we primarily utilized a combination of tumor/normal WES and tumor RNA-seq,” writes co-senior author Andrew Kung, M.D., Ph.D., from Columbia University (New York). “This platform provided several advantages over targeted cancer gene panels, including the ability to identify translocations, segmental chromosomal changes, and relative gene expression changes.”
After filtering, the researchers identified a total of 180 reportable mutations and 20 fusions (110 mutations from solid tumor samples with a mean of 2.91 aberrations per sample and 90 mutations from hematologic samples with a mean of 5.2 aberrations per sample). Potentially actionable alterations were identified in 21 of 65 patients with solid tumors and 17 of 36 patients with hematologic conditions. Yet, only 16 percent of these patients subsequently received matched therapy. The authors say the lack of data in pediatric populations is a known “constraint” to applying targeted therapies in the pediatric setting. “Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful,” the authors write.
For further discussion of this study, see “Special Focus” in the March issue of Diagnostic Testing & Emerging Technologies.
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