https://repositorio.fleni.org.ar/xmlui/handle/123456789/84 2026-06-27T00:23:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1505 Frontotemporal dementia: Clinical aspects, genetics, and neuropathology of a family with a C9ORF72 expansion in Argentina Román, Karen Daniela; Ardohain, Carolina Agata; Surace, Ezequiel Ignacio; Mezmezian, Mónica Beatriz; Levy, Alejandro; Baez Lovera, Alice; Turizo, Carlos; Sorbara, Marcos G.; Esnaola y Rojas, María M.; Graviotto, Gastón H.; Sevlever, Gustavo Emilio; Allegri, Ricardo Francisco; Serrano, Cecilia M.; Magrath Guimet, Nahuel Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia, typically manifesting before the age of 65, with a mean onset at 58 years. FTD may encompass a spectrum of neurodegenerative disorders resulting from frontotemporal lobar degeneration (FTLD), affecting behavior, language, and motor function. Among its clinical variants, the behavioral variant (bvFTD) is the most frequently inherited, often associated with mutations in MAPT, GRN, and C9ORF72, the latter being the most prevalent genetic cause of FTD and FTD-motor neuron disease (FTD-MND). While bvFTD is classically defined by profound behavioral changes and executive dysfunction, cases linked to C9ORF72 expansions exhibit atypical neuropsychiatric features. This study documents two cases within the same family presenting with bvFTD and atypical parkinsonism, associated with a C9ORF72 expansion. Neurocognitive assessments, genetic testing, and neuroimaging (MRI, SPECT) were performed to characterize the clinical phenotype. A detailed review of the familial aggregation of neurodegenerative and psychiatric disorders provided further insight into the genetic contributions to symptomatology. The findings highlight the phenotypic heterogeneity associated with C9ORF72 expansions, demonstrating a spectrum ranging from bvFTD to atypical parkinsonism, with variable neuropsychiatric involvement. While movement disorders in FTD have historically been underestimated, these cases reinforce the association between parkinsonism and familial bvFTD. Given the limited epidemiological data on genetic FTD in Latin America, this study underscores the importance of genetic testing in cases with prominent behavioral and psychiatric symptoms, supporting early identification and genetic counseling for affected families. 2026-01-07T00:00:00Z 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