Document Detail

Screening of RB1 alterations in Brazilian patients with retinoblastoma and relatives with retinoma: phenotypic and genotypic associations.
MedLine Citation:
PMID:  23532519     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To identify constitutional alterations of the retinoblastoma 1 gene (RB1) in two cohorts of Brazilian patients with retinoblastoma and to analyze genotype-phenotype associations.
METHODS: Molecular screening was carried out by direct sequencing of the 27 RB1 exons and flanking regions in blood DNA of 71 patients with retinoblastoma and 4 relatives with retinoma, and with multiplex ligation-dependent probe amplification (MLPA) in 21 patients. The presumed impact of nucleotide substitutions on the structure of the retinoblastoma protein (pRB) was predicted by Polymorphism Phenotyping-2 (PolyPhen-2). Kaplan-Meier and log-rank test were used for estimating 60-month survival rates.
RESULTS: One hundred two nucleotide substitutions were detected, 92 substitutions in 59 patients with retinoblastoma and 10 substitutions in 4 individuals with retinoma. Eight substitutions were novel. The majority of substitutions were intronic (86.2%). More than one substitution was present in 37.3% of patients. Twenty-one duplications and 11 deletions were found in 12 patients; some of which with both types of alterations. Duplications/deletions were found in four patients lacking constitutional alterations when analyzed by sequencing, and in eight patients carrying one or more polymorphic intronic substitutions. The global 60-month survival rate in patients was 91.8% (Confidence Interval95% = 85.0 - 99.1). Significant, lower survival rates were found in extraocular presentation (81.0%) versus intraocular tumors (P = 0.014), first enucleation after 1 month following diagnosis (80.9%) versus earlier first enucleation (P = 0.020), and relapse (100.0%) versus absence of relapse (P = 0.0005).
CONCLUSIONS: Fifteen substitutions (4 intronic and 11 exonic) were identified as probably or likely pathogenic. Four of these 11 exonic substitutions were novel. Survival rates, however, were not affected by presence of these probably or likely pathogenic alterations, most of which not found in patients with retinoblastoma from other Latin American countries. These differences might be related to the different ethnic composition of the Latin American cohorts. Portuguese Abstract.
Raquel H Barbosa; Fernanda C C Aguiar; Morgana F L Silva; Regis A Costa; Fernando R Vargas; Evandro Lucena; Mírian Carvalho de Souza; Liz Maria de Almeida; Camila Bittar; Patrícia Ashton Prolla; Cibele R Bonvicino; Héctor N Seuánez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-05-07
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-08     Completed Date:  2013-07-10     Revised Date:  2013-08-08    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3184-94     Citation Subset:  IM    
Genetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
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MeSH Terms
Brazil / epidemiology
Child, Preschool
Exons / genetics
Genes, Retinoblastoma / genetics*
Genetic Association Studies*
Introns / genetics
Middle Aged
Multiplex Polymerase Chain Reaction
Mutation, Missense*
Polymerase Chain Reaction
Retinal Neoplasms / genetics*,  mortality,  pathology
Retinoblastoma / genetics*,  mortality,  pathology
Retinoblastoma Protein / genetics*
Sequence Analysis, DNA
Survival Rate
Young Adult
Reg. No./Substance:
0/Retinoblastoma Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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