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Concomitant KIAA1549-BRAF fusion and IDH mutation in Pediatric spinal cord astrocytoma: a case report and literature review

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Abstract

Primary tumors of the spinal cord are rare, accounting for 3–6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed to difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicating a tentative diagnosis of astrocytoma. The patient underwent resection of the lesion in the spinal canal from the cervical 6 level to the thoracic 2 level. Histopathology confirmed diagnosis of astrocytoma, WHO grade 2. Genetic analysis showed both IDH1 R132H mutation and KIAA1549-BRAF fusion. Therefore, our integrated diagnosis was astrocytoma, IDH mutation, WHO grade 2. Its molecular analyses include IDH1 R132H mutation and KIAA1549-BRAF fusion. After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.

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References

  1. Badiali M, Gleize V, Paris S, Moi L, Elhouadani S, Arcella A, Morace R, Antonelli M, Buttarelli FR, Figarella-Branger D, Kim YH, Ohgaki H, Mokhtari K, Sanson M, Giangaspero F (2012) KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults. Brain Pathol 22:841–847

    Article  CAS  Google Scholar 

  2. Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A (2008) Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol 116:597–602

    Article  CAS  Google Scholar 

  3. Behling F, Schittenhelm J (2019) Oncogenic BRAF Alterations and Their Role in Brain Tumors. Cancers (Basel) 11:794

  4. Cruz GR, Dias Oliveira I, Moraes L, Del Giudice PM, de Seixas Alves MT, Capellano AM, Saba-Silva N, Cavalheiro S, Cerutti JM, Toledo SR (2014) Analysis of KIAA1549-BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas. J Neurooncol 117:235–242

    Article  CAS  Google Scholar 

  5. Ellezam B, Theeler BJ, Walbert T, Mammoser AG, Horbinski C, Kleinschmidt-DeMasters BK, Perry A, Puduvalli V, Fuller GN, Bruner JM, Aldape KD (2012) Low rate of R132H IDH1 mutation in infratentorial and spinal cord grade II and III diffuse gliomas. Acta Neuropathol 124:449–451

    Article  Google Scholar 

  6. Gierke M, Sperveslage J, Schwab D, Beschorner R, Ebinger M, Schuhmann MU, Schittenhelm J (2016) Analysis of IDH1-R132 mutation, BRAF V600 mutation and KIAA1549-BRAF fusion transcript status in central nervous system tumors supports pediatric tumor classification. J Cancer Res Clin Oncol 142:89–100

    Article  CAS  Google Scholar 

  7. Helen Davies GRB, Cox C, Stephens P et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954

    Article  Google Scholar 

  8. Hirano K, Imagama S, Sato K, Kato F, Yukawa Y, Yoshihara H, Kamiya M, Deguchi M, Kanemura T, Matsubara Y, Inoh H, Kawakami N, Takatsu T, Ito Z, Wakao N, Ando K, Tauchi R, Muramoto A, Matsuyama Y, Ishiguro N (2012) Primary spinal cord tumors: review of 678 surgically treated patients in Japan. A multicenter study. Eur Spine J 21:2019–2026

    Article  Google Scholar 

  9. Javadi SA, Hartmann C, Walter GF, Banan R, Samii A (2018) IDH1 mutation in brain stem glioma: case report and review of literature. Asian J Neurosurg 13:414–417

    Article  Google Scholar 

  10. Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, Collins VP (2008) Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–8677

    Article  CAS  Google Scholar 

  11. Kloosterhof NK, Bralten LBC, Dubbink HJ, French PJ, van den Bent MJ (2011) Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma? Lancet Oncol 12:83–91

    Article  CAS  Google Scholar 

  12. Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, Pfister S, von Deimling A, Hartmann C (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405

    Article  CAS  Google Scholar 

  13. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820

    Article  Google Scholar 

  14. Matsumura N, Ikota H, Yamazaki T, Nakata S, Nobusawa S, Hirato J, Yoshimoto Y, Yokoo H (2018) Cerebellar high-grade astrocytoma with IDH mutations in the elderly: A report of two cases. Neuropathology 38:411–416

  15. Maurer G, Tarkowski B, Baccarini M (2011) Raf kinases in cancer-roles and therapeutic opportunities. Oncogene 30:3477–3488

    Article  CAS  Google Scholar 

  16. Oka H, Utsuki S, Tanizaki Y, Hagiwara H, Miyajima Y, Sato K, Kusumi M, Kijima C, Fujii K (2013) Clinicopathological features of human brainstem gliomas. Brain Tumor Pathol 30:1–7

    Article  Google Scholar 

  17. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS (2019) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro Oncol 21:v1–v100

    Article  Google Scholar 

  18. Penman CL, Faulkner C, Lowis SP, Kurian KM (2015) Current Understanding of BRAF alterations in diagnosis, prognosis, and therapeutic targeting in pediatric low-grade gliomas. Front Oncol 5:54

    Article  Google Scholar 

  19. Porkholm M, Raunio A, Vainionpaa R, Salonen T, Hernesniemi J, Valanne L, Satopaa J, Karppinen A, Oinas M, Tynninen O, Pentikainen V, Kivivuori SM (2018) Molecular alterations in pediatric brainstem gliomas. Pediatr Blood Cancer 65. https://doi.org/10.1002/pbc.26751

  20. Ryall S, Zapotocky M, Fukuoka K et al (2020) Integrated molecular and clinical analysis of 1,000 pediatric low-grade gliomas. Cancer Cell 37(569–583):e565

    Google Scholar 

  21. Schellinger KA, Propp JM, Villano JL, McCarthy BJ (2008) Descriptive epidemiology of primary spinal cord tumors. J Neurooncol 87:173–179

    Article  Google Scholar 

  22. Shankar GM, Lelic N, Gill CM, Thorner AR, Van Hummelen P, Wisoff JH, Loeffler JS, Brastianos PK, Shin JH, Borges LF, Butler WE, Zagzag D, Brody RI, Duhaime AC, Taylor MD, Hawkins CE, Louis DN, Cahill DP, Curry WT, Meyerson M (2016) BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology. Acta Neuropathol 131:147–150

    Article  Google Scholar 

  23. Takai K, Tanaka S, Sota T, Mukasa A, Komori T, Taniguchi M (2017) Spinal cord astrocytoma with isocitrate dehydrogenase 1 gene mutation. World Neurosurg 108:991 e913–991 e916

  24. Tatevossian RG, Lawson AR, Forshew T, Hindley GF, Ellison DW, Sheer D (2010) MAPK pathway activation and the origins of pediatric low-grade astrocytomas. J Cell Physiol 222:509–514

    CAS  PubMed  Google Scholar 

  25. Tran NH, Wu X, Frost JA (2005) B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms. J Biol Chem 280:16244–16253

    Article  CAS  Google Scholar 

  26. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  CAS  Google Scholar 

  27. Yang RR, Aibaidula A, Wang WW, Chan AK, Shi ZF, Zhang ZY, Chan DTM, Poon WS, Liu XZ, Li WC, Zhang RQ, Li YX, Chung NY, Chen H, Wu J, Zhou L, Li KK, Ng HK (2018) Pediatric low-grade gliomas can be molecularly stratified for risk. Acta Neuropathol 136:641–655

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Dr. Li Liu and Dr. Lihong zhao from the Department of pathology, Xuanwu hospital for technical support, as well as Weiwei Zhang and Limeng Xie for help.

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Correspondence to Yueshan Piao.

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Sun, M., Wang, L., Lu, D. et al. Concomitant KIAA1549-BRAF fusion and IDH mutation in Pediatric spinal cord astrocytoma: a case report and literature review. Brain Tumor Pathol 38, 132–137 (2021). https://doi.org/10.1007/s10014-021-00394-2

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  • DOI: https://doi.org/10.1007/s10014-021-00394-2

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