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Radiation-induced gliomas: a report of four cases and analysis of molecular biomarkers

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Abstract

Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs. Immunohistochemical (IHC) staining for isocitrate dehydrogenase 1 (IDH1), p53, alpha thalassemia/mental retardation syndrome X-linked (ATRX), and H3K27M, and direct DNA sequencing of IDH1/2, telomerase reverse transcriptase (TERT) promoter, Histone H3.3 (H3F3A) and B-Raf (BRAF) genes was performed. All tumor specimens were IDH1-, p53- and H3K27M-negative. The nuclei of tumor cells in all cases exhibited positive staining for ATRX. In direct DNA sequencing analysis, no IDH1, IDH2, TERT promoter, H3F3A or BRAF mutations were found in any of the cases. Our findings suggest that these characteristic glioma-associated molecular mutations may be rare events in RIGs. More RIGs need to be tested for analysis of molecular biomarkers to clarify the clinical and histopathological spectra of this tumor.

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References

  1. Matsutani M (2001) Japanese Pediatric Brain Tumor Study Group. Combined chemotherapy and radiation therapy for CNS germ cell tumors—the Japanese experience. J Neurooncol 54:311–316

    Article  CAS  PubMed  Google Scholar 

  2. Clark AJ, Cage TA, Aranda D, Parsa AT, Sun PP, Auguste KI, Gupta N (2013) A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma. Childs Nerv Syst 29:231–238

    Article  PubMed  Google Scholar 

  3. Elsamadicy AA, Babu R, Kirkpatrick JP, Adamson DC (2015) Radiation-induced malignant gliomas: a current review. World Neurosurg 83:530–542

    Article  PubMed  Google Scholar 

  4. Yan H, Parsons DW, ** 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  PubMed  PubMed Central  Google Scholar 

  5. Takano S, Ishikawa E, Sakamoto N, Matsuda M, Akutsu H, Noguchi M, Kato Y, Yamamoto T, Matsumura A (2016) Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas. Brain Tumor Pathol 33:107–116

    Article  CAS  PubMed  Google Scholar 

  6. Solomon DA, Wood MD, Tihan T, Bollen AW, Gupta N, Phillips JJ, Perry A (2016) Diffuse midline gliomas with histone H3-K27M mutation: a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations. Brain Pathol 26:569–580

    Article  CAS  PubMed  Google Scholar 

  7. Aihara K, Mukasa A, Gotoh K, Saito K, Nagae G, Tsuji S, Tatsuno K, Yamamoto S, Takayanagi S, Narita Y, Shibui S, Aburatani H, Saito N (2014) H3F3A K27M mutations in thalamic gliomas from young adult patients. Neuro Oncol 16:140–146

    Article  CAS  PubMed  Google Scholar 

  8. Gielen GH, Gessi M, Hammes J, Kramm CM, Waha A, Pietsch T (2013) H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas. Am J Clin Pathol 139:345–349

    Article  CAS  PubMed  Google Scholar 

  9. 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  PubMed  Google Scholar 

  10. Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL (1998) Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer 82:8–34

    Article  CAS  PubMed  Google Scholar 

  11. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ebrahimi A, Skardelly M, Bonzheim I, Ott I, Mühleisen H, Eckert F, Tabatabai G, Schittenhelm J (2016) ATRX immunostaining predicts IDH and H3F3A status in gliomas. Acta Neuropathol Commun 4:60

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bechet D, Gielen GG, Korshunov A, Pfister SM, Rousso C, Faury D, Fiset PO, Benlimane N, Lewis PW, Lu C, David Allis C, Kieran MW, Ligon KL, Pietsch T, Ellezam B, Albrecht S, Jabado N (2014) Specific detection of methionine 27 mutation in histone 3 variants (H3K27M) in fixed tissue from high-grade astrocytomas. Acta Neuropathol 128:733–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tanaka S, Nakada M, Nobusawa S, Suzuki SO, Sabit H, Miyashita K, Hayashi Y (2014) Epithelioid glioblastoma arising from pleomorphic xanthoastrocytoma with the BRAF V600E mutation. Brain Tumor Pathol 31:172–176

    Article  PubMed  Google Scholar 

  15. Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, Schmieder K, Wesseling P, Mawrin C, Hasselblatt M, Louis DN, Korshunov A, Pfister S, Hartmann C, Paulus W, Reifenberger G, von Deimling A (2014) Absence of TERT promoter mutations in primary melanocytic tumours of the central nervous system. Neuropathol Appl Neurobiol 40:794–797

    Article  Google Scholar 

  16. Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174:1149–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Arai M, Nobusawa S, Ikota H, Takemura S, Nakazato Y (2012) Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. Brain Tumor Pathol 29:201–206

    Article  CAS  PubMed  Google Scholar 

  18. Nagaishi M, Nobusawa S, Yokoo H, Sugiura Y, Tsuda K, Tanaka Y, Suzuki K, Hyodo A (2016) Genetic mutations in high grade gliomas of the adult spinal cord. Brain Tumor Pathol 33:267–269

    Article  PubMed  Google Scholar 

  19. Yang SY, Wang KC, Cho BK, Kim YY, Lim SY, Park SH, Kim IH, Kim SK (2005) Radiation-induced cerebellar glioblastoma at the site of a treated medulloblastoma: case report. J Neurosurg 102:417–422

    CAS  PubMed  Google Scholar 

  20. Gessi M, Maderna E, Guzzetti S, Cefalo G, Massimino M, Solero CL, Finocchiaro G, Pollo B (2008) Radiation-induced glioblastoma in a medulloblastoma patient: a case report with molecular features. Neuropathology 28:633–639

    PubMed  Google Scholar 

  21. Brat DJ, James CD, Jedlicka AE, Connolly DC, Chang E, Castellani RJ, Schmid M, Schiller M, Carson DA, Burger PC (1999) Molecular genetic alterations in radiation-induced astrocytomas. Am J Pathol 154:1431–1438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Takami H, Yoshida A, Fukushima S, Arita H, Matsushita Y, Nakamura T, Ohno M, Miyakita Y, Shibui S, Narita Y, Ichimura K (2015) Revisiting TP53 mutations and immunohistochemistry—a comparative study in 157 diffuse gliomas. Brain Pathol 25:256–265

    Article  CAS  PubMed  Google Scholar 

  23. Mascelli S, Raso A, Biassoni R, Severino M, Sak K, Joost K, Milanaccio C, Barra S, Grillo-Ruggieri F, Vanni I, Consales A, Cama A, Capra V, Nozza P, Garrè ML (2012) Analysis of NADP+-dependent isocitrate dehydrogenase-1/2 gene mutations in pediatric brain tumors: report of a secondary anaplastic astrocytoma carrying the IDH1 mutation. J Neurooncol 109:477–484

    Article  CAS  PubMed  Google Scholar 

  24. Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, Fontebasso AM, Fleming A, Hadjadj D, Schwartzentruber J, Majewski J, Dong Z, Siegel P, Albrecht S, Croul S, Jones DT, Kool M, Tonjes M, Reifenberger G, Faury D, Zadeh G, Pfister S, Jabado N (2012) Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol 124:615–625

    Article  CAS  PubMed  Google Scholar 

  25. Koelsche C, Sahm F, Capper D, Reuss D, Sturm D, Jones DT, Kool M, Northcott PA, Wiestler B, Böhmer K, Meyer J, Mawrin C, Hartmann C, Mittelbronn M, Platten M, Brokinkel B, Seiz M, Herold-Mende C, Unterberg A, Schittenhelm J, Weller M, Pfister S, Wick W, Korshunov A, von Deimling A (2013) Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. Acta Neuropathol 126:907–915

    Article  CAS  PubMed  Google Scholar 

  26. Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, Schmieder K, Wesseling P, Mawrin C, Hasselblatt M, Louis DN, Korshunov A, Pfister S, Hartmann C, Paulus W, Reifenberger G, von Deimling A (2011) Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397–405

    Article  CAS  PubMed  Google Scholar 

  27. Yamanaka R, Hayano A, Kanayama T (2016) Radiation-induced gliomas: a comprehensive review and meta-analysis. Neurosurg Rev. doi:10.1007/s10143-016-0786-8 (Epub ahead of print)

    Google Scholar 

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Acknowledgements

The authors wish to thank Ms. Erika Komura for her invaluable assistance with the pathological study.

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Correspondence to Yasuo Sasagawa.

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Nakao, T., Sasagawa, Y., Nobusawa, S. et al. Radiation-induced gliomas: a report of four cases and analysis of molecular biomarkers. Brain Tumor Pathol 34, 149–154 (2017). https://doi.org/10.1007/s10014-017-0292-x

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  • DOI: https://doi.org/10.1007/s10014-017-0292-x

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