Abstract
BackgroundAnaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment.Case presentationOur patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were FANCD2, NF1, FANCA, FANCI, and WRN. Even though TP53 presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore, in silico analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient’s variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma.ConclusionsNext-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient’s variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.
Highlights
ConclusionsNext-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that target the patient’s variants
Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide
On January 21, 2020, the patient was admitted to the emergency room. She presented with severe headache and vomiting, normal vital signs, without neurological deterioration or signs of endocranial hypertension. She was treated with opioids, and contrast-enhanced magnetic resonance imaging (MRI) of the brain showed an increase of the tumor size, which extended to the corpus callosum and left entorhinal cortex
Summary
NGS approaches for identifying cancer-related DNA alterations are routinely used in developed countries. Developing countries, such as Ecuador, are far from the use of this technology in clinical practice. Using NGS approaches, we found that our patient had an extensive family history of a dominant inheritance syndrome; had the family known this information sooner, it might have helped them foresee the development of AA (Fig. 1) This is only an example of how many syndromes and rare diseases are misdiagnosed, and molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment
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