JCO Precision Oncol: NTRK fusion is more common in childhood tumors than expected

The rearfraging codes involving the neurotrophic tyrosine-intrinsic kinase (NTRK) genes NTRK1, NTRK2, and NTRK3 contain fusion proteins in the complete NTRK kinase domain, which is the carcinogenic driver of different tumors in histology.
NTRK rearm involves dozens of genes that have been described and lead to unmodulated composition of active TRK kinases and downstream pathways.
In children, NTRK fusion has a high incidence of certain tumors, such as infant fibroblastoma (IF), congenital mesothelioma and secretion cancer, while in children with thyroid papillomas and some childhood gliomas, NTRK fusion rates are low (5%-26%).
, NTRK fusion is rarely found in gastrointestinal mesothelioma, melanoma, lung adenocarcinoma, acute leukemia, and soft tissue sarcoma, with a range of histological forms.
in a large study of childhood cancer patients published recently in the journal JCO Precision Oncology, researchers at Children's Hospital of Philadelphia (CHOP) analyzed the frequency, fusion partners, and clinical outcomes of the neurotrophic factor tyrosine-subject kinase (NTRK), a clinical biomarker that identifies patients suitable for treatment with FDA-approved TRK inhibitors.
researchers found that NTRK fusion is more common in childhood tumors than adult tumors and involves a wider range of tumors, which helps prioritize screening of NTRK fusion in children with cancer who may benefit from TRK inhibitor treatment.
previous studies have shown that the NTRK gene re-ranks in a variety of cancers that drive tumor growth.
this led to the development of the first generation of oral NTRK inhibitors larotrectinib and entrectinib, and facilitated the development of other NTRK inhibitors, which are currently under clinical development.
ongoing clinical trials to determine the best use of these drugs in children.
Taking into account that certain cancers, such as infant fibroblastoma (IF) and secretion cancer, have a high incidence of NTRK fusion in children, while other cancers such as melanoma and acute leukemia rarely involve NTRK fusion, the researchers are trying to better understand how often these genes are fused in all childhood cancers.
, they analyzed 1,347 consecutive child tumors in 1,217 patients who performed tumor genome analysis using custom-designed DNA and RNA next-generation sequencing panels.
researchers found NTRK fusion in 29 tumors in 27 patients, with a positive rate of 2.22 percent for all tumors and 3.08 percent for solid tumors.
NTRK fusion detected 13% detection rate in thyroid papilloma (PTCs), 1.9% detection rate in central nervous system (CNS) tumors, 1.8% detection rate in non-CNS, non-PTC solid tumors, and 0.4% detection rate in hematosomas. Molecular studies of NTRK fusion-positive patients in
CHOP cohorts summarized the study's follow-up of patients for up to 46 months, and in almost all cases, NTRK fusion tests confirmed the diagnosis of lesion types, with the final diagnosis of five tumors based primarily on the discovery of NTRK fusion.
in one patient, the diagnosis changes due to NTRK fusion.
in another case, a 6-month-old baby who had a lump in his upper left limb due to IF and needed very complex surgery to remove it was treated with larotrectinib and received complete pathological remission.
the morphological and immunological chemistry characteristics of soft tissue NTRK fusion tumors, the researchers studied the spectrum of NTRK-positive child tumors in the largest un selected group of children's tumors to date and found that NTRK fusion was present in 2.22 percent of all tumors and 3.08 percent of solid tumors.
study of 1,217 patients, NTRK fusion was more common in childhood tumors than in adult tumors, and involved a wider range of fusion companion groups and childhood tumors than previously recognized.
identification of these NTRK fusions helps with accurate cancer diagnosis and targeted treatment of TRK inhibitors, emphasizing the clinical application of screening NTRK fusion for all childhood tumors.
: Xiaonan Zhao, Chelsea Kotch, Elizabeth Fox, Lea F. Surrey, Gerald B. Wertheim, Zubair W. Baloch, Fumin Lin, Vinodh Pillai, Minjie Luo, Portia A. Kreiger, Jennifer E. Pogorier, Rebecca L. Linn, Pierre A. Russo, Mariarita Santi, Adam C. Resnick, Phil B. Storm, Stephen P. NTRK Fusions Identified in Pediatric Tumors: The Frequency, Fusion Partners, and Clinical Outcome. JCO Precision Oncology, 2021; (5): 204 DOI: 10.1200/PO.20.00250MedSci Original Source: MedSci Original Copyright Notice: All noted on this website "Source: Met Medical Or "Source: MedSci Original" text, images and audio-visual materials, copyrights are owned by Metz Medicine, without authorization, no media, website or individual may reproduce, authorized to reproduce with the words "Source: Mets Medicine".
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