Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile

• Authors: NUSSBAUMER Gunther; BENESCH Martin; GRABOVSKA Yura; MACKAY Alan; CASTEL David; GRILL Jacques; ALONSO Marta M; ANTONELLI Manila; BAILEY Simon; BAUGH Joshua N; BIASSONI Veronica; BLATTNER-JOHNSON Mirjam; BRONISCER Alberto; CARAI Andrea; COLAFATI Giovanna Stefania; COLDITZ Niclas; CORBACIOGLU Selim; CRAMPSIE Shauna; ENTZ-WERLE Natacha; EYRICH Matthias; FRIKER Lea L; FRÜHWALD Michael C; GARRE Maria Luisa; GERBER Nicolas U; GIANGASPERO Felice; GIL-DA-COSTA Maria J; GRAF Norbert; HARGRAVE Darren; HAUSER Peter; HERRLINGER Ulrich; HOFFMANN Marion; HULLEMAN Esther; IZQUIERDO Elisa; JACOBS Sandra; KARREMANN Michael; KATTAMIS Antonis; KEBUDI Rejin; ROLF-DIETER Kortmann; KWIECIEN Robert; MASSIMINO Maura; MASTRONUZZI Angela; MIELE Evelina; MORANA Giovanni; NOACK Claudia M; PENTIKAINEN Virve; PERWEIN Thomas; PFISTER Stefan M; PIETSCH Torsten; ROKA Kleoniki; ROSSI Sabrina; RUTKOWSKI Stefan; SCHIAVELLO Elisabetta; SEIDEL Clemens; ŠTĚRBA Jaroslav; STURM Dominik; SUMERAUER David; TACKE Anna; TEMELSO Sara; VALENTINI Chiara; VUURDEN Dannis van; VARLET Pascale; ZANTEN Sophie E M Veldhuijzen van; VINCI Maria; BUEREN André O von; WARMUTH-METZ Monika; WESSELING Pieter; WIESE Maria; WOLFF Johannes E A; ZAMECNIK Josef; MADRID Andrés Morales La; BISON Brigitte; GIELEN Gerrit H; JONES David T W; JONES Chris; KRAMM Christof M
• Year of publication: 2024
• Type: Article in Periodical
• Magazine / Source: NEURO-ONCOLOGY
• MU Faculty or unit: Faculty of Medicine
• web: https://academic.oup.com/neuro-oncology/article/26/9/1723/7667099
• Doi: http://dx.doi.org/10.1093/neuonc/noae080
• Keywords: chromosome 6; gliomatosis cerebri; H3-wild-type and IDH-wild-type; pedHGG_RTK2; pediatric-type glioma; pediatric-type high-grade glioma
• Description: Background The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established. Methods We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. Results Median overall survival (OS) was 15.5 months (interquartile range, 10.9–27.7) with a 2-year survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2–55.7); grade III: 15.9 months (11.4–26.3); grade IV: 10.4 months (8.8–14.4). By DNA methylation profiling (n = 49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wild-type (n = 31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n = 19), pedHGG_A/B (n = 6), and pedHGG_MYCN (n = 5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wild-type subgroup, recurrent alterations in EGFR (n = 10) and BCOR (n = 9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wild-type subgroup TP53 alterations had a significant negative effect on OS. Conclusions Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).