Shedding Light on the Landscape of NTRK Aberrations in Pediatric and Adult Tumors
Posted: Sunday, August 1, 2021
Published in JCO Precision Oncology, Razelle Kurzrock, MD, of Moores Cancer Center, University of California, San Diego, and colleagues reported their analysis of the prevalence of all NTRK alterations—copy number alterations, mutations, increased transcript expression, and fusions—in pediatric and adult cancers to gain a better understanding of the implications for NTRK-targeted therapeutics. Based on data from more than 13,000 tumor samples, about 14% were affected by NTRK alterations, although NTRK fusions were observed in 31 of 9,966 adult tumors and 12 of 3,501 pediatric tumors.
“The rarity of NTRK fusions, but their remarkable tractability in multiple cancer types, further expands the paradigm of tissue-agnostic genomic drug development,” commented the study authors.
A total of 17 tumor types across 3,501 samples from the St. Jude PeCan database and 33 tumor types across 9,966 samples from The Cancer Genome Atlas were obtained for analysis. In addition, the investigators used the Pediatric Cancer Genome Project and The Jackson Laboratory Tumor Fusion Gene Data Portal to identify NTRK fusions, along with transcriptomic and genomic co-aberrations in various tumor types.
In 0.34% of pediatric tumors and 0.31% of adult tumors, NTRK fusions were observed. In children, fusions occurred most commonly in pediatric melanoma (11.1%), glioma (3.97%), and B-cell acute lymphoblastic leukemia (0.14%). In adults, however, the most common NTRK fusions occurred in thyroid cancer (2.34%), colon adenocarcinoma (0.97%), and low-grade glioma (0.94%).
Transcriptomic and genomic NTRK aberrations such as amplification, mRNA overexpression, and mutations were identified in 14.2% of samples. The frequency of changes that involved the NTRK receptors ranged from 4.1% to 6.2%. The co-receptor p75NTR presented alterations in nearly 5% of samples; variations in ligands were observed in 3.8% to 5.4% of samples. Of note, co-alterations in adult samples frequently occurred, usually involving cell-cycle machinery, mitogen-activated protein kinase signals, the downstream phosphoinositide-3-kinase signaling pathway, and other tyrosine kinase receptors.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.