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Journal of Medical Case Reports
Published in: Journal of Medical Case Reports 1/2020

Open Access 01-12-2020 | Astrocytoma | Case report

A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocytoma: a case report

Authors: Jennyfer M. García-Cárdenas, Ana Karina Zambrano, Patricia Guevara-Ramírez, Santiago Guerrero, Gabriel Runruil, Andrés López-Cortés, Jorge P. Torres-Yaguana, Isaac Armendáriz-Castillo, Andy Pérez-Villa, Verónica Yumiceba, Paola E. Leone, César Paz-y-Miño

Published in: Journal of Medical Case Reports | Issue 1/2020

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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.
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Literature
1.
2.
Burzynski SR, Burzynski GS, Marszalek A, Janicki TJ, Martinez-Canca JF. Long-term survival over 21 years and pathologically confirmed complete response in pediatric anaplastic astrocytoma: a case report. J Neurol Stroke. 2015;2(6):00072.
3.
Braunstein S, Raleigh D, Bindra R, Mueller S, Haas-Kogan D. Pediatric high-grade glioma: current molecular landscape and therapeutic approaches. J Neurooncol. 2017;134:541–9.PubMed
4.
Killela PJ, Pirozzi CJ, Reitman ZJ, Jones S, Rasheed BA, Lipp E, et al. The genetic landscape of anaplastic astrocytoma. Oncotarget. 2014;5(6):1452–7.PubMed
5.
Leone PE, González MB, Elosua C, Gómez-Moreta JA, Lumbreras E, Robledo C, et al. Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme. Ann Surg Oncol. 2012;19:2367–79.PubMed
6.
Hoffman LM, Salloum R, Fouladi M. Molecular biology of pediatric brain tumors and impact on novel therapies. Curr Neurol Neurosci Rep. 2015;15(4):10.PubMed
7.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
8.
9.
Dang M, Phillips PC. Pediatric brain tumors. Continuum (Minneap Minn). 2017;23(6, Neuro-oncology):1727–57.
10.
Perkins SM, Rubin JB, Leonard JR, Smyth MD, El Naqa I, Michalski JM, et al. Glioblastoma in children: a single-institution experience. Int J Radiat Oncol. 2011;80:1117–21.
11.
Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, et al. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro Oncol. 2011;13:317–23.PubMedPubMedCentral
12.
Korones DN, Smith A, Foreman N, Bouffet E. Temozolomide and oral VP-16 for children and young adults with recurrent or treatment-induced malignant gliomas. Pediatr Blood Cancer. 2006;47:37–41.PubMed
13.
Kline CN, Joseph NM, Grenert JP, Van Ziffle J, Talevich E, Onodera C, et al. Targeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy. Neuro Oncol. 2017;19:699–709.PubMed
14.
Nikiforova MN, Wald AI, Melan MA, Roy S, Zhong S, Hamilton RL, et al. Targeted next-generation sequencing panel (GlioSeq) provides comprehensive genetic profiling of central nervous system tumors. Neuro Oncol. 2016;18:379–87.PubMed
15.
Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, et al. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014;46:444–50.PubMedPubMedCentral
16.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20.PubMed
17.
Johnson A, Severson E, Gay L, Vergilio JA, Elvin J, Suh J, et al. Comprehensive genomic profiling of 282 pediatric low- and high-grade gliomas reveals genomic drivers, tumor mutational burden, and hypermutation signatures. Oncologist. 2017;22:1478–90.PubMedPubMedCentral
18.
19.
20.
21.
Zambrano AK, Gaviria A, Cobos-Navarrete S, Gruezo C, Rodríguez-Pollit C, Armendáriz-Castillo I, et al. The three-hybrid genetic composition of an Ecuadorian population using AIMs-InDels compared with autosomes, mitochondrial DNA and Y chromosome data. Sci Rep. 2019;9:9247.PubMedPubMedCentral
22.
Guerrero S, López-Cortés A, Indacochea A, García-Cárdenas JM, Zambrano AK, Cabrera-Andrade A, et al. Analysis of racial/ethnic representation in select basic and applied cancer research studies. Sci Rep. 2018;8:13978.PubMedPubMedCentral
23.
Arora RS, Alston RD, Eden TOB, Estlin EJ, Moran A, Birch JM. Age–incidence patterns of primary CNS tumors in children, adolescents, and adults in England. Neuro Oncol. 2009;11:403–13.PubMedPubMedCentral
24.
1000 Genomes Project Consortium, Abecasis GR, Auton A, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65.
25.
International HapMap Consortium, Frazer KA, Ballinger DG, et al. A second generation human haplotype map of over 3.1 million SNPs. Nature. 2007;449(7164):851–61.
26.
Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.
27.
Weinstein JN, Collisson EA, Mills GB, Shaw KRM, Ozenberger BA, Ellrott K, et al. The cancer genome atlas pan-cancer analysis project. Nat Genet. 2013;45:1113–20.PubMedPubMedCentral
28.
Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA, Easton J, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med. 2015;373:2336–46.PubMedPubMedCentral
29.
30.
Sinha I, Jones L, Smyth RL, Williamson PR. A systematic review of studies that aim to determine which outcomes to measure in clinical trials in children. PLoS Med. 2008;5(4):e96.PubMedPubMedCentral
31.
Rocchi F, Tomasi P. The development of medicines for children: part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni. Pharmacol Res. 2011;64(3):169–75.PubMed
32.
Monti P, Perfumo C, Bisio A, Ciribilli Y, Menichini P, Russo D, et al. Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. Mol Cancer Res. 2011;9:271–9.PubMedPubMedCentral
33.
Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, et al. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci U S A. 2003;100:8424–9.PubMedPubMedCentral
34.
Parsons DW, Roy A, Yang Y, Wang T, Scollon S, Bergstrom K, et al. Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol. 2016;2:616–24.PubMedPubMedCentral
35.
36.
Li FP, Fraumeni JF, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988;48:5358–62.PubMed
37.
McBride KA, Ballinger ML, Killick E, Kirk J, Tattersall MHN, Eeles RA, et al. Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat Rev Clin Oncol. 2014;11:260–71.PubMed
38.
Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016;17:1295–305.PubMed
39.
Birch JM, Hartley AL, Tricker KJ, Prosser J, Condie A, Kelsey AM, et al. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res. 1994;54:1298–304.PubMed
40.
Schneider K, Zelley K, Nichols KE, Garber J. Li-Fraumeni syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews. Seattle: University of Washington, Seattle; 1993.
41.
Zampiga V, Danesi R, Tedaldi G, Tebaldi M, Cangini I, Pirini F, et al. Multiple primary tumors in a family with Li-Fraumeni syndrome with a TP53 germline mutation identified by next-generation sequencing. Int J Biol Markers. 2016;31:461–5.
42.
Chompret A, Abel A, Stoppa-Lyonnet D, Brugiéres L, Pagés S, Feunteun J, et al. Sensitivity and predictive value of criteria for p53 germline mutation screening. J Med Genet. 2001;38:43–7.PubMedPubMedCentral
Metadata
Title
A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocytoma: a case report
Authors
Jennyfer M. García-Cárdenas
Ana Karina Zambrano
Patricia Guevara-Ramírez
Santiago Guerrero
Gabriel Runruil
Andrés López-Cortés
Jorge P. Torres-Yaguana
Isaac Armendáriz-Castillo
Andy Pérez-Villa
Verónica Yumiceba
Paola E. Leone
César Paz-y-Miño
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2020
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-020-02451-4

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