| Author | Coelho, Karoline Brito Caetano Andrade | |
| Author | Squire, Jeremy A. | |
| Author | Duarte, Kelly Gomes | |
| Author | Sares, Cláudia Tarcila Gomes | |
| Author | Moreda, Natalia Alonso | |
| Author | Pereira, Jonatas Luiz | |
| Author | Silva, Israel Tojal da | |
| Author | Defelicibus, Alexandre | |
| Author | Aoki, Mateus Nóbrega | |
| Author | Rivas, Javier de las | |
| Author | Reis, Rodolfo Borges dos | |
| Author | Zanette, Dalila Lucíola | |
| Access date | 2024-04-23T19:51:18Z | |
| Available date | 2024-04-23T19:51:18Z | |
| Document date | 2024 | |
| Citation | COELHO, Karoline Brito Caetano Andrade et al. Germline variants in early and late-onset Brazilian prostate cancer patients. Urologic Oncology: Seminars and Original Investigations., v. 42, p. 68-76, 2024. | en_US |
| ISSN | 1078-1439 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/63628 | |
| Language | por | en_US |
| Publisher | Elsevier | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Início tardio | en_US |
| Subject in Portuguese | Início precoce | en_US |
| Title | Germline variants in early and late-onset Brazilian prostate cancer patients | en_US |
| Type | Article | en_US |
| DOI | https://doi.org/10.1016/j.urolonc.2024.01.015 | |
| Abstract | The median age for Prostate Cancer (PCa) diagnosis is 66 years, but 10% are diagnosed before 55 years. Studies on earlyonset PCa remain both limited and controversial. This investigation sought to identify and characterize germline variants within Brazilian PCa patients classified as either early or later onset disease.Peripheral blood DNA from 71 PCa patients: 18 younger (≤ 55 years) and 53 older (≥ 60 years) was used for Targeted DNA sequencing of 20 genes linked to DNA damage response, transcriptional regulation, cell cycle, and epigenetic control. Subsequent genetic variant identification was performed and variant functional impacts were analyzed with in silico prediction. A higher frequency of variants in the BRCA2 and KMT2C genes across both age groups. KMT2C has been linked to the epigenetic dysregulation observed during disease progression in PCa. We present the first instance of KMT2C mutation within the blood of Brazilian PCa patients. Furthermore, out of the recognized variants within the KMT2C gene, 7 were designated as deleterious. Thirteen deleterious variants were exclusively detected in the younger group, while the older group exhibited 37 variants. Within these findings, 4 novel variants emerged, including 1 designated as pathogenic.Our findings contribute to a deeper understanding of the genetic factors associated with PCa susceptibility in different age groups, especially among the Brazilian population. This is the first investigation to explore germline variants specifically in younger Brazilian PCa patients, with high relevance given the genetic diversity of the population in Brazil. Additionally, our work presents evidence of functionally deleterious germline variants within the KMT2C gene among Brazilian PCa patients. The identification of novel and functionally significant variants in the KMT2C gene emphasizes its potential role in PCa development and warrants further investigation. | en_US |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil. / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Genética. Ribeirão Preto, SP, Brasil. / Department of Pathology and Molecular Medicine. Queen’s University. Kingston, ON, Canada. | en_US |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Cancer Research Center. Consejo Superior de Investigaciones Cientíıficas and University of Salamanca. Salamanca, Spain. | en_US |
| Affilliation | Erasto Gaertner Hospital. Paraná, Brasil. | en_US |
| Affilliation | Laboratory of Computational Biology and Bioinformatics, CIPE / A.C. Camargo Cancer Center. São Paulo, Brasil. | en_US |
| Affilliation | Laboratory of Computational Biology and Bioinformatics, CIPE / A.C. Camargo Cancer Center. São Paulo, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil. | en_US |
| Affilliation | Cancer Research Center. Consejo Superior de Investigaciones Cientíıficas and University of Salamanca. Salamanca, Spain. | en_US |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil. | en_US |
| Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil. | en_US |
| Subject | Prostate cancer | en_US |
| Subject | Prostatic Neoplasms | en_US |
| Subject | Germline variants | en_US |
| Subject | Germ Cells | en_US |
| Subject | Sequence Analysis, DNA | en_US |
| Subject | Early-onset | en_US |
| Subject | Late-onset | en_US |
| Subject in Spanish | Neoplasias de la Próstata | en_US |
| Subject in Spanish | Células Germinativas | en_US |
| Subject in Spanish | Análisis de Secuencia de ADN | en_US |
| Subject in French | Tumeurs de la prostate | en_US |
| Subject in French | Cellules germinales | en_US |
| Subject in French | Analyse de séquence d'ADN | en_US |
| DeCS | Neoplasias da Próstata | en_US |
| DeCS | Células Germinativas | en_US |
| DeCS | Análise de Sequência de DNA | en_US |
