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https://www.arca.fiocruz.br/handle/icict/39246
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ArtigoDireito Autoral
Acesso restrito
Data de embargo
2022-01-01
Coleções
- IOC - Artigos de Periódicos [12642]
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A MOLECULAR STUDY OF FIRST AND SECOND RB1 MUTATIONAL HITS IN RETINOBLASTOMA PATIENTS
Autor(es)
Afiliação
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-Graduação em Biologia Celular e Molecular. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer. Programa de Pós-Graduação em Oncologia. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Serviço de Pediatria. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Patologia. Rio de Janeiro, RJ, Brasil.
Hospital de Servidores do Estado. Serviço de Oftalmologia. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer. Programa de Pós-Graduação em Oncologia. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Serviço de Pediatria. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Patologia. Rio de Janeiro, RJ, Brasil.
Hospital de Servidores do Estado. Serviço de Oftalmologia. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Genética. Rio de Janeiro, RJ, Brasil.
Resumo em Inglês
RB1 mutations accountable for biallelic inactivation are crucial events in the development of retinoblastoma because a first mutation (M1) predisposes to retinoblastoma while a second mutation (M2) is required for tumor development. Mutational analyses of this gene showed a wide spectrum of genetic alterations (single base substitutions, insertions, or deletions, as well as small and large deletions). The most frequent second hit in retinoblastoma patients is loss of heterozygosity (LOH) followed by promoter methylation. Molecular analyses of RB1 mutations were conducted in 36 patients (20 unilateral and 16 bilateral) using polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP) analysis, sequencing, and LOH analysis. Sixty-four amplified fragments showing abnormal SSCP patterns were sequenced, and mutations were confirmed in five patients (13.89%). Four mutations were located at coding regions, and a fifth one was found at an exon-intron junction. Two mutations were C-->T transitions, two were small-length deletions, and one was a G-->A transition. A total of 47.05% patients showed LOH. In one patient, the parental origin of the mutated allele was detected: the allele retained in the tumor was the paternal one. This work helps to characterize the spectrum of mutations in the Brazilian population, and to confirm that formaldehyde-fixed paraffin tissue can provide valuable information on the RB1 status in retinoblastoma patients.
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