TUMOUR BIOLOGY
Authors: T. Geller, V. Prakash, J. Batanian, M. Guzman, E. Duncavage, T. Gershon, A. Crowther, J. Wu, H. Liu, F. Fang, I. Davis, D. Tripolitsioti, M. Ma, K. Kumar, J. Grahlert, K. Egli, G. Fiaschetti, T. Shalaby, M. Grotzer, M. Baumgartner, M. Braoudaki, G. I. Lambrou, K. Giannikou, V. Millionis, S. A. Papadodima, N. Settas, G. Sfakianos, K. Stefanaki, A. Kattamis, C. A. Spiliopoulou, F. Tzortzatou-Stathopoulou, E. Kanavakis, S. Gholamin, S. Mitra, A. Feroze, M. Zhang, R. Esparza, S. Kahn, C. Richard, A. Achrol, A. Volkmer, J. Liu, J. Volkmer, R. Majeti, I. Weissman, S. Cheshier, K. Bhatia, N. Brown, J. Teague, P. Lo, J. Challis, V. Beshay, M. Sullivan, F. Mechinaud, J. Hansford, M. Z. Arifin, R. H. Dahlan, M. Sobana, P. Saputra, M. T. Tisell, A. Danielsson, H. Caren, R. Bhardwaj, M. Chakravadhanula, C. Hampton, V. Ozals, J. Georges, W. Decker, V. Kodibagkar, A. Nguyen, M. Legrain, M. P. Gaub, E. Pencreach, M. P. Chenard, D. Guenot, N. Entz-Werle, Y. Kanemura, K. Ichimura, T. Shofuda, R. Nishikawa, M. Yamasaki, S. Shibui, H. Arai, J. Xia, A. Brian, R. Prins, C. Pennell, C. Moertel, M. Olin, L. Bie, X. Zhang, H. Liu, M. Olsson, T. Kling, S. Nelander, V. Biassoni, I. Bongarzone, P. Verderio, M. Massimino, R. Magni, S. Pizzamiglio, C. Ciniselli, E. Taverna, M. De Bortoli, A. Luchini, L. Liotta, E. Barzano, F. Spreafico, E. Visse, E. Sanden, A. Darabi, P. Siesjo, S. Jackson, K. Cohen, D. Lin, P. Burger, F. Rodriguez, X. Yao, R. Liucheng, L. Qin, T. Na, W. Meilin, Z. Zhengdong, F. Yongjun, S. Pfeifer, M. Nister, T. D. de Stahl, E. Basmaci, E. Orphanidou-Vlachou, M.-A. Brundler, Y. Sun, N. Davies, M. Wilson, X. Pan, T. Arvanitis, R. Grundy, A. Peet, C. Eden, B. Ju, T. Phoenix, B. Nimmervoll, Y. Tong, D. Ellison, C. Lessman, M. Taylor, R. Gilbertson, V. Folgiero, F. del Bufalo, A. Carai, M. G. Cefalo, A. Citti, S. Rutella, F. Locatelli, A. Mastronuzzi, O. Maher, S. Khatua, W. Zaky, A. Lourdusamy, L. Meijer, R. Layfield, R. Grundy, D. T. W. Jones, D. Capper, M. Sill, V. Hovestadt, L. Schweizer, P. Lichter, D. Zagzag, M. A. Karajannis, K. D. Aldape, A. Korshunov, A. von Deimling, S. Pfister, A. Chakrabarty, R. Feltbower, E. Sheridon, H. Hassan, M. Shires, S. Picton, K. Hatziagapiou, M. Braoudaki, G. I. Lambrou, F. Tsorteki, F. Tzortzatou-Stathopoulou, K. Bethanis, V. Gemou-Engesaeth, S. N. Chi, P. Bandopadhayay, K. Janeway, N. Pinches, H. Malkin, M. W. Kieran, P. E. Manley, A. Green, L. Goumnerova, S. Ramkissoon, M. H. Harris, K. L. Ligon, U. Kahlert, M. Suarez, J. Maciaczyk, E. Bar, C. Eberhart, R. Kenchappa, N. Krishnan, P. Forsyth, B. McKenzie, A. Pisklakova, G. McFadden, R. Kenchappa, P. Forsyth, W. Pan, L. Rodriguez, J. Glod, J. M. Levy, J. Thompson, A. Griesinger, V. Amani, A. Donson, D. Birks, M. Morgan, M. Handler, N. Foreman, A. Thorburn, R. R. Lulla, J. Laskowski, J. Fangusaro, A. J. DiPatri, T. Alden, T. Tomita, E. F. Vanin, S. Goldman, M. B. Soares, M. Remke, V. Ramaswamy, X. Wang, F. Jorgensen, A. S. Morrissy, M. Marra, R. Packer, E. Bouffet, S. Pfister, N. Jabado, M. Taylor, B. Cole, E. Rudzinski, M. Anderson, K. Bloom, A. Lee, S. Leary, G. Leprivier, M. Remke, B. Rotblat, S. Agnihotri, M. Kool, B. Derry, S. Pfister, M. D. Taylor, P. H. Sorensen, T. Dobson, E. Busschers, H. Taylor, R. Hatcher, J. Fangusaro, R. Lulla, S. Goldman, V. Rajaram, C. Das, V. Gopalakrishnan
Journal: Neuro-Oncology (2014)

DIG (Desmoplastic Infantile Ganglioglioma) is a rare intracranial neoplasm classified as WHO grade I tumor under neuronal and mixed neuronal glial tumors (under 2007 World Health Organization brain tumor classification).It is usually considered to have a good prognosis but 40% of the cases require additional medical, radiation and/or further surgical intervention and 15% of infants and children develop leptomeningeal spread or die from DIG.We report a case of DIG presenting at 2 mo of age that showed aggressive behavior, requiring debulking at 2.5 mo age and subsequently at 10 mo age following a tumor recurrence.Chemotherapy following surgery was successful in suppressing the tumor growth for 7.5 yrs.He then presented with malignant transformation into glioblastoma.Successful debulking followed by chemotherapy was given.At 1 yr follow up, the child had moderate neurological deficits but had a subsequent rapid progression and died.Chromosome microarray analysis (CMA) using oligo array performed on the biopsy specimen obtained at 2 mo age did not show any significant abnormality.However, CMA of the glioblastoma was very abnormal showing significant genomic deletions and duplications.Genomic next generation sequencing showed a somatic single nucleotide non-synonymous variant, p.R248Q in Exon 7 of TP53 in the primary DIG and the GBM tumors.The non-synonymous variant in TP53 gene is predicted to be deleterious, altering the structure of the L2/L3 motif of the DNA binding domain tp53 protein.The TP53 gene which is a known primary site of genetic alteration that predisposes to malignant tumors provides a reason for the transformation of DIG to glioblastoma in our case.Therefore, molecular genetic testing is recommended on some DIG tumors which may provide a prognostic biological marker.