Letícia Ganem Rillo Paz Barateiro, Rodrigo de Oliveira Cavagna, Mariana Bisarro Dos Reis, Flávia Escremim de Paula, Gustavo Ramos Teixeira, Daniel Antunes Moreno, Murilo Bonatelli, Iara Santana, Fabiano Pinto Saggioro, Luciano Neder, João Norberto Stavale, Suzana Maria Fleury Malheiros, Hernan Garcia-Rivello, Silvia Christiansen, Susana Nunes, Maria João Gil da Costa, Jorge Pinheiro, Carlos Almeida Júnior, Bruna Minniti Mançano, Rui Manuel Reis
{"title":"拉丁美洲-伊比利亚髓母细胞瘤体细胞突变谱分析及驱动基因的临床影响：迈向精准医疗。","authors":"Letícia Ganem Rillo Paz Barateiro, Rodrigo de Oliveira Cavagna, Mariana Bisarro Dos Reis, Flávia Escremim de Paula, Gustavo Ramos Teixeira, Daniel Antunes Moreno, Murilo Bonatelli, Iara Santana, Fabiano Pinto Saggioro, Luciano Neder, João Norberto Stavale, Suzana Maria Fleury Malheiros, Hernan Garcia-Rivello, Silvia Christiansen, Susana Nunes, Maria João Gil da Costa, Jorge Pinheiro, Carlos Almeida Júnior, Bruna Minniti Mançano, Rui Manuel Reis","doi":"10.1111/neup.12979","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>SHH</sub>, 13.0% MB<sub>WNT</sub>, 7.3% MB<sub>Grp3</sub>, and 13.0% MB<sub>Grp4</sub>. 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<sub>SHH</sub> 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<sub>SHH</sub>, 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.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.\",\"authors\":\"Letícia Ganem Rillo Paz Barateiro, Rodrigo de Oliveira Cavagna, Mariana Bisarro Dos Reis, Flávia Escremim de Paula, Gustavo Ramos Teixeira, Daniel Antunes Moreno, Murilo Bonatelli, Iara Santana, Fabiano Pinto Saggioro, Luciano Neder, João Norberto Stavale, Suzana Maria Fleury Malheiros, Hernan Garcia-Rivello, Silvia Christiansen, Susana Nunes, Maria João Gil da Costa, Jorge Pinheiro, Carlos Almeida Júnior, Bruna Minniti Mançano, Rui Manuel Reis\",\"doi\":\"10.1111/neup.12979\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>SHH</sub>, 13.0% MB<sub>WNT</sub>, 7.3% MB<sub>Grp3</sub>, and 13.0% MB<sub>Grp4</sub>. 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<sub>SHH</sub> 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<sub>SHH</sub>, 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.</p>\",\"PeriodicalId\":19204,\"journal\":{\"name\":\"Neuropathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-05-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/neup.12979\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/neup.12979","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Somatic mutational profiling and clinical impact of driver genes in Latin-Iberian medulloblastomas: Towards precision medicine.
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 MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. 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 MBSHH 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 MBSHH, 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.
期刊介绍：
Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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