A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocyt
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(2020) 14:136
CASE REPORT
Open Access
A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocytoma: a case report Jennyfer M. García-Cárdenas1, Ana Karina Zambrano1, Patricia Guevara-Ramírez1, Santiago Guerrero1, Gabriel Runruil2, Andrés López-Cortés1, Jorge P. Torres-Yaguana1, Isaac Armendáriz-Castillo1, Andy Pérez-Villa1, Verónica Yumiceba1, Paola E. Leone1 and César Paz-y-Miño1*
Abstract Background: 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. 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 presentation: Our 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. Conclusions: Next-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. Keywords: Pediatric anaplastic astrocytoma, High-grade gliomas, TP53, Li-Fraumeni syndrome
* Correspondence: [email protected] 1 Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provi
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