A germline variant of TP53 in paediatric diffuse leptomeningeal glioneuronal tumour
- 34 Downloads
Diffuse leptomeningeal glioneuronal tumour (DLGNT) is an extremely rare tumour involving the neuroaxis. At present, its exact pathogenesis and associated factors remain incompletely characterised. Recent molecular investigations in a small cohort have offered some insights into this disease. However, the role of germline findings has not yet been fully explored in affected patients. The authors present a case of DLGNT, focusing on the clinical and molecular features with reference to current disease knowledge.
A 4-year-old male presented with raised intracranial pressure symptoms secondary to extensive leptomeningeal disease of the brain and spine. Preliminary impression was that of an inflammatory lesion.
A lumbar biopsy of the lesion confirmed DLGNT on routine diagnostic examination. Further molecular analysis of his tumour and blood demonstrated a previously unreported TP53 exon 5 (c.147V > I) germline variant. Based on the latest DLGNT molecular subtyping classification, his tumour falls into the group with better clinical outcome. However, his germline findings may add an extra layer of uncertainty to his overall prognosis.
Given that much remains unknown in many rare paediatric tumours at this stage, isolated findings found in an individual may be of significance. Supplementary genetic information, together with tumour molecular analysis, add to our current understanding of this uncommon disease. This case highlights the benefit of combined clinical and molecular efforts, including germline testing, especially for children affected by such challenging neoplasms.
KeywordsGlioma Diffuse leptomeningeal glioneuronal tumour TP53
This project was supported by the VIVA-KKH Paediatric Brain and Solid Tumour Programme. In addition, the authors would like to thank Dr. Alvin Lim and Miss Lim TH from the Cytogenetics Laboratory, Department of Molecular Pathology (Singapore General Hospital), for their kind assistance with the FISH images.
Compliance with ethical standards
Conflict of interest
We, the authors of this manuscript, report no funding, financial support or industrial affiliations received for the writing of this article. In addition, we report no conflict of interest concerning the material or methods used in this paper. This manuscript has not been published and is not being considered for publication elsewhere.
- 1.Schniederjan MJ, Alghamdi S, Castellano-Sanchez A, Mazewski C, Brahma B, Brat DJ, Brathwaite CD, Janss AJ (2013) Diffuse leptomeningeal neuroepithelial tumor: 9 pediatric cases with chromosome 1p/19q deletion status and IDH1 (R132H) immunohistochemistry. Am J Surg Pathol 37:763–771CrossRefGoogle Scholar
- 4.Lyle MR, Dolia JN, Fratkin J, Nichols TA, Herrington BL (2015) Newly identified characteristics and suggestions for diagnosis and treatment of diffuse leptomeningeal glioneuronal/neuroepithelial tumors: a case report and review of the literature. Child Neurol Open 2:2329048X14567531CrossRefGoogle Scholar
- 5.Dodgshun AJ, SantaCruz N, Hwang J, Ramkissoon SH, Malkin H, Bergthold G, Manley P, Chi S, MacGregor D, Goumnerova L, Sullivan M, Ligon K, Beroukhim R, Herrington B, Kieran MW, Hansford JR, Bandopadhayay P (2016) Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation. J Neuro-Oncol 128:293–302CrossRefGoogle Scholar
- 6.Deng MY, Sill M, Chiang J, Schittenhelm J, Ebinger M, Schuhmann MU, Monoranu CM, Milde T, Wittmann A, Hartmann C, Sommer C, Paulus W, Gartner J, Bruck W, Rudiger T, Leipold A, Jaunmuktane Z, Brandner S, Giangaspero F, Nozza P, Mora J, Morales la Madrid A, Cruz Martinez O, Hansford JR, Pietsch T, Tietze A, Hernaiz-Driever P, Stoler I, Capper D, Korshunov A, Ellison DW, von Deimling A, Pfister SM, Sahm F, Jones DTW (2018) Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol 136:239–253CrossRefGoogle Scholar
- 7.Goodman AM, Choi M, Wieduwilt M, Mulroney C, Costello C, Frampton G, Miller V, Kurzrock R (2017) Next generation sequencing reveals potentially actionable alterations in the majority of patients with lymphoid malignancies. JCO Precis Oncol 1:1–13Google Scholar
- 8.Johnson DB, Frampton GM, Rioth MJ, Yusko E, Xu Y, Guo X, Ennis RC, Fabrizio D, Chalmers ZR, Greenbowe J, Ali SM, Balasubramanian S, Sun JX, He Y, Frederick DT, Puzanov I, Balko JM, Cates JM, Ross JS, Sanders C, Robins H, Shyr Y, Miller VA, Stephens PJ, Sullivan RJ, Sosman JA, Lovly CM (2016) Targeted next generation sequencing identifies markers of response to PD-1 blockade. Cancer Immunol Res 4:959–967CrossRefGoogle Scholar
- 9.Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF (2012) Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children’s Oncology Group. J Clin Oncol 30:2641–2647CrossRefGoogle Scholar
- 10.Dodgshun AJ, Maixner WJ, Heath JA, Sullivan MJ, Hansford JR (2016) Single agent carboplatin for pediatric low-grade glioma: a retrospective analysis shows equivalent efficacy to multiagent chemotherapy. Int J Cancer 138:481–488Google Scholar
- 12.Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, von Deimling A (2016) WHO classification of tumours of the central nervous system. IARC, LyonGoogle Scholar
- 14.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 121:397–405CrossRefGoogle Scholar
- 16.Preuss M, Christiansen H, Merkenschlager A, Hirsch FW, Kiess W, Muller W, Kastner S, Henssler A, Pekrun A, Hauch H, Nathrath M, Meixensberger J, Pietsch T, Kuchelmeister K (2015) Disseminated oligodendroglial-like leptomeningeal tumors: preliminary diagnostic and therapeutic results for a novel tumor entity [corrected]. J Neuro-Oncol 124:65–74CrossRefGoogle Scholar