https://repositorio.fleni.org.ar/xmlui/handle/123456789/83 2026-04-05T18:47:46Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1450 Impact of 10q loss, CDKN2A deletions, EGFR amplification, and trisomy of chromosome 7 in the overall survival of IDH-mutant astrocytoma Mezmezian, Mónica Beatriz; Arakaki, Naomi; Diez, Blanca; Martinetto, Horacio; Sevlever, Gustavo Emilio Introduction: Since progression from grade 2 to grade 4 occurs in the evolution of IDH-mutant astrocytoma (A, IDH-mut), it is crucial to identify the key factors that define the different grades. Aims: To evaluate the impact on overall survival (OS) of molecular alterations traditionally associated with high-grade gliomas within the grading scheme. Materials and methods: We retrospectively analyzed the role of 10q loss, CDKN2A deletions, EGFR amplification (Amp), and trisomy of chromosome 7 (trisomy 7) in 189 A, IDH-mut, reclassified according to the WHO 2021 criteria (grade 2, n = 133; grade 3, n = 18; grade 4, n = 38). Results: Among the 189 cases, 29 presented with CDKN2A hemizygous deletion (hemidel), 17 with CDKN2A homozygous deletion, 18 showed trisomy 7, and 2 showed EGFR Amp. A multivariate test revealed that WHO grade 4 and trisomy 7 significantly impacted OS. CDKN2A hemidel and 10q loss did not influence OS in our cohort. Given that 11 out of 18 cases with trisomy 7 were IDH-mutant grade 2 (G2), we compared G2 cases with and without trisomy 7 and found worse OS in cases with trisomy (p = 0.0034), similar to WHO grade 4. Conclusion: Our results suggest that trisomy 7 plays a significant role in the OS of A, IDH-mut. Further research is needed to determine whether trisomy 7 is an independent marker or if it is associated with other molecular alterations that affect OS. 2025-08-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1386 The Immunogenic Tumor-Specific Neoantigen Database (ITSNdb): A Tool for Comprehensive Performance Evaluation of Neoantigen Immunogenicity Predictors Nibeyro, Guadalupe; Flesia, Rocío; Orschanski, Daniela; Nava, Agustín; Baronetto, Verónica; Fernández, Elmer A. The identification of tumor-specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based antitumoral vaccines and/or adoptive T cell immunotherapies. In silico immunogenicity prediction of candidate peptides is crucial to speed up the prioritization of such peptides for experimental validation. Up to now, several methods were proposed as TSN immunogenicity predictors, but there are still several drawbacks in both performance and comprehensive performance evaluation, mainly due to the absence of well documented and adequate TSN databases.The Immunogenic Tumor-Specific Neoantigen database (ITSNdb) is a tool developed to fairly benchmark immunogenicity predictors intended to be used over tumoral neopeptides. The proposed ITSNdb enables the analysis of immunogenicity without the interference of other variables such as binding affinity or peptide processing, as they were considered into the inclusion criteria for the curation of neoantigens. ITSNdb, together with a dataset emulating a true patient neoantigens scenario, as a validation strategy for prioritization, and a list of neopeptides predicted to bind to major histocompatibility complex I (MHC-I) from immune checkpoint blockade immunotherapy (ICB) cohorts, along with their associated patient outcomes, is available to evaluate tumor neoantigen burden as a biomarker for ICB response (accessible at https://github.com/elmerfer/ITSNdb). 2025-01-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1203 Identification of a putative molecular subtype of adult-type diffuse astrocytoma with recurrent MAPK pathway alterations Sievers, Philipp; Bielle, Franck; Göbel, Kirsten; Schrimpf, Daniel; Nichelli, Lucia; Mathon, Bertrand; Appay, Romain; Boldt, Henning B.; Dohmen, Hildegard; Selignow, Carmen; Acker, Till; Vicha, Ales; Martinetto, Horacio; Schweizer, Leonille; Schüller, Ulrich; Brandner, Sebastian; Wesseling, Pieter; Schmid, Simone; Capper, David; Abdullaev, Zied; Aldape, Kenneth; Korshunov, Andrey; Krieg, Sandro M.; Wick, Wolfgang; Pfister, Stefan M.; von Deimling, Andreas; Reuss, David E.; Jones, David T.W.; Sahm, Felix 2024-07-18T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1135 Hyaline eosinophilic astrocytic inclusions in two children with drug-resistant epilepsy—Case reports and literature review Mezmezian, Mónica Beatriz; Arakaki, Naomi; Yáñez, Paulina; Arias Cebollada, Eugenia; Muro, Valeria L.; Sevlever, Gustavo Emilio Introduction: Hyaline eosinophilic astrocytic inclusion (HEAI) is a rare histological finding in cases with drugresistant epilepsy (DRE). Objectives: To describe two cases of DRE with HEAI and review the literature. Patients and Methods: Case 1: A 5-year-old boy with a history of DRE since 5 months of age and global developmental delay, nonverbal (GDD, NV). MRI revealed signs of polymicrogyria, involving the right frontal operculum with an abnormal cortical folding and rotation pattern. The genetic panel showed a variant of uncertain significance in the SCL2A1 gene. Outcome: Engel IV-B. Case 2: A 5-year-old boy with a history of DRE since 4 months of age and GDD, NV. MRI showed abnormal cortical folding and cortical thickening in the right frontal lobe. Genetic testing demonstrated a variant of uncertain significance in the ADAR gene. Outcome: Engel IV-A. Resection of the lesion was performed in both patients. Results: Both cases showed brightly eosinophilic structures within the astrocytic cytoplasm in the gray matter and FCD type 2A. The inclusions were negative with PAS and Congo red. By immunohistochemistry, they were positive for S100 and negative for vimentin, and GFAP. We also analyzed the data of all the previously reported cases. Conclusion: HEAI is a rare entity, with only 53 cases reported, including our cases. Evaluating all the cases, the average age at seizure onset of pediatric patients (n = 48) was 7 months, without sex predilection. Seven patients had Aicardi syndrome, and 23 patients presented GDD. Seizures were observed in 47 patients. Outcome Engel: I in 10 cases, II in 5, III in 9, and IV in 9. Most cases involved the frontal lobe (n = 40). HEAIs were positive for S100 in 21/25 (84%), filamin in 22/25 (88%), GFAP in 3/32 cases (9%), vimentin in 1/16 (6%), and PAS in 3/21 (14%). FCD was observed in 19/50 patients (38%). The significance of HEAI is not clear. Genetic studies of the surgical specimens will probably allow a better comprehension of this entity. 2023-09-13T00:00:00Z