2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Diagnostic dilemma in a pediatric high grade brain tumor with the <em>ETV6</em>-<em>NTRK3</em> gene fusion

Pdf Summary

Neurotrophic tyrosine receptor kinase (NTRK) fusions have been identified as oncogenic drivers in various pediatric tumors. These fusions result in constitutively active chimeric receptors. NTRK fusions have been detected at varying frequencies in pediatric cancers, including central nervous system (CNS) tumors. However, CNS tumors with NTRK fusions are rare and have been mainly reported in gliomas or mixed neuronal glial tumors. <br /><br />The case presented describes a 3-month-old female who presented with abnormal movements, crying, and unresponsiveness. Imaging revealed a large mass lesion in the brain, which was surgically removed. Pathological analysis initially diagnosed the tumor as choroid plexus carcinoma. Further genetic analysis confirmed the presence of the ETV6-NTRK3 fusion and identified the tumor as infant-type hemispheric glioma. <br /><br />The case raises the question of whether reclassification of the tumor diagnosis is necessary as molecular testing becomes more advanced and available. The patient is currently disease-free following surgery and chemotherapy. If the tumor were to relapse, targeted therapy for NTRK fusion tumors could be considered, as clinical trials have shown promising results with inhibitors such as Larotrectinib.<br /><br />Infant-type hemispheric gliomas (IHG) are high-grade astrocytomas that occur in the cerebral hemispheres of young children. They often harbor RTK fusions, including those involving NTRK family members or other genes like ROS1, ALK, or MET. IHG have a better prognosis compared to other pediatric high-grade gliomas, and copy number alterations are rare.<br /><br />This case highlights the clinical, pathological, and molecular heterogeneity of CNS tumors with NTRK fusions. It also suggests the potential for targeted therapies in these rare tumors.

Asset Subtitle

Presenting Author - Elena A. Repnikova, PhD; Co-Author - Kenneth Aldape, MD; Co-Author - Midhat S. Farooqi, MD, PhD; Co-Author - Melissa Gener, MD; Co-Author - Kevin Ginn, MD; Co-Author - Yelisey Romanov, HSE; Co-Author - Alexander Kats, MD;

Meta Tag

Cancer Cytogenetics

Chromosomal Abnormalities

Clinical Applications of Molecular Cytogenetics

Cytogenetics

Microarray

Molecular Cytogenetics

Pathology

Co-Author Kenneth Aldape, MD

Co-Author Midhat S. Farooqi, MD, PhD

Co-Author Melissa Gener, MD

Co-Author Kevin Ginn, MD

Co-Author Yelisey Romanov, HSE

Co-Author Alexander Kats, MD

Presenting Author Elena A. Repnikova, PhD

Keywords

NTRK fusions

pediatric tumors

constitutively active chimeric receptors

CNS tumors

gliomas

ETV6-NTRK3 fusion

infant-type hemispheric glioma

targeted therapy

Larotrectinib

rare tumors