Genetic profile of low-grade diffuse glioma in patients followed at the National Cancer Institute between 2009 and 2015.

Abstract

e14020 Background: In Brazil, approximately 11,490 new cases of malignant Central Nervous System (CNS) tumors are expected between 2023 and 2025. Historically, classification was based on histopathological features and cell type. Advances in molecular biology led the World Health Organization (WHO) to update the CNS tumor classification in 2021, incorporating genomic markers that improve the definition of diffuse glioma subtypes, impacting prognosis and treatment. However, in Brazil, immunohistochemistry testing is hampered by a lack of antibodies in public oncology centers, and genetic sequencing is limited by high costs, specialized equipment, and trained personnel for execution and interpretation. This study aimed to investigate the genetic profile of WHO grade 2 diffuse gliomas diagnosed between 2009 and 2015 at the National Cancer Institute using a custom panel. Methods: This retrospective, descriptive, unicentric study included patients over 18 years of age and was approved by the Research Ethics Committee. Medical records and institutional archives (2009–2015) were evaluated to collect clinical, sociodemographic, and treatment data. Histopathological reports were reviewed by two pathologists, and tumor samples underwent immunohistochemistry to detect IDH1 (R132H) mutations, ATRX, p53, Ki67 and immunological markers, such as CD4, CD8, PD-1, PD-L1, and TREM2. Variant analysis was conducted using a custom 39-gene panel (Agilent Technologies) sequenced on the NovaSeq6000 platform (Illumina). Results: Of the 66 patients initially selected, 40 met eligibility criteria, and 29 had tumor samples available for analysis. Among the 20 patients analyzed (12 men, 8 women), 17 were under 40 years of age. A total of 91 genetic variants were identified, of which 9 were silent, and 82 presented significant alterations. Missense mutations accounted for the majority (90%), followed by frameshift deletions (5%) and nonsense mutations (3%). Most variants were single nucleotide polymorphisms (SNPs, n = 77), with 4 deletions (DEL) and 1 double nucleotide polymorphism (DNP). The most frequent base substitution was cytosine (C) to thymine (T) (n = 61), followed by cytosine (C) to adenine (A) (n = 10). IDH1 (R132H) mutations were the most prevalent (67%), followed by FAT1 (38%), MTOR (33%), NOTCH1 (29%), and CIC (29%). Additional mutations included NF1 (24%), FAT2 (24%), EGFR (19%), PDGFRA (14%), and NF2 (14%), with a single IDH2 mutation detected. Conclusions: The study highlights the genetic profile of low-grade gliomas, promoting more precise tumor evaluation. Future analyses will address the tumor immune microenvironment, copy number variations, structural alterations, and tumor reclassification per WHO guidelines. Additionally, a virtual panel will analyze the TCGA dataset to compare this cohort's molecular characteristics with global data, broadening its relevance.