Barateiro Letícia Ganem Rillo Paz, de Oliveira Cavagna Rodrigo, Dos Reis Mariana Bisarro, de Paula Flávia Escremim, Teixeira Gustavo Ramos, Moreno Daniel Antunes, Bonatelli Murilo, Santana Iara, Saggioro Fabiano Pinto, Neder Luciano, Stavale João Norberto, Malheiros Suzana Maria Fleury, Garcia-Rivello Hernan, Christiansen Silvia, Nunes Susana, da Costa Maria João Gil, Pinheiro Jorge, Júnior Carlos Almeida, Mançano Bruna Minniti, Reis Rui Manuel
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
Molecular Diagnostic Laboratory, Barretos Cancer Hospital, Barretos, Brazil.
Neuropathology. 2025 Feb;45(1):30-37. doi: 10.1111/neup.12979. Epub 2024 May 12.
Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MB, 13.0% MB, 7.3% MB, and 13.0% MB. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MB tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MB, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.
髓母细胞瘤（MB）是儿童中最常见的恶性脑肿瘤，以其异质性和治疗相关毒性而闻名，迫切需要新的治疗靶点。我们使用Illumina TruSight Tumor 15检测板分析了69例拉丁 - 伊比利亚分子特征明确的髓母细胞瘤中15个驱动基因的体细胞突变谱。我们根据变异的临床影响和致癌性对其进行分类。在患者中，66.7%为MB，13.0%为MB，7.3%为MB，13.0%为MB。在所发现的63个变异中，54%被分类为I/II级，31.7%为致癌/可能致癌。我们观察到33.3%的病例至少携带一种突变。TP53（23.2%，16/69）是突变最多的基因，其次是PIK3CA（5.8%，4/69）、KIT（4.3%，3/69）、PDGFRA（2.9%，2/69）、EGFR（1.4%，1/69）、ERBB2（1.4%，1/69）和NRAS（1.4%，1/69）。约41%的MB肿瘤表现出突变，TP53（32.6%）是最常突变的基因。I/II级和致癌/可能致癌的TP53变异与复发、进展和较低的生存率相关。在PIK3CA和KIT基因中鉴定出了潜在的可操作变异。拉丁 - 伊比利亚髓母细胞瘤，特别是MB，比其他人群表现出更高的突变频率。我们证实TP53突变状态是一个重要的预后因素，而PIK3CA和KIT是潜在的治疗靶点。
