RESUMO
Retinoblastoma is the most common paediatric neoplasm of the retina, and one of the earliest model of cancer genetics since the identification of the master tumour suppressor gene RB1. Tumorigenesis has been shown to be driven by pathogenic variants of the RB1 locus, but also genomic and epigenomic alterations outside the locus. The increasing knowledge on this "mutational landscape" is used in current practice for precise genetic testing and counselling. Novel methods provide access to pre-therapeutic tumour DNA, by isolating cell-free DNA from aqueous humour or plasma. This is expected to facilitate assessment of the constitutional status of RB1, to provide an early risk stratification using molecular prognostic markers, to follow the response to the treatment in longitudinal studies, and to predict the response to targeted therapies. The aim of this review is to show how molecular genetics of retinoblastoma drives diagnosis, treatment, monitoring of the disease and surveillance of the patients and relatives. We first recap the current knowledge on retinoblastoma genetics and its use in every-day practice. We then focus on retinoblastoma subgrouping at the era of molecular biology, and the expected input of cell-free DNA in the field.
Assuntos
Neoplasias da Retina , Retinoblastoma , Criança , Humanos , Retinoblastoma/genética , Genes do Retinoblastoma , Mutação , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Assistência ao Paciente , Análise Mutacional de DNA/métodosRESUMO
No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Lipocalin 2 (LCN2 or NGAL), alone or complexed with MMP-9 (NGAL/MMP-9), is increased in several retinal disorders. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched healthy controls (n = 130). Samples with CRP > 5 mg/L, creatinine > 100 µmol/L, and/or urea > 7.5 mmol/L were excluded. Serum LCN2 was lower in CSCR patients than controls (81.4 ± 48.7 vs 107.3 ± 44.5 ng/ml, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.006). Serum NGAL/MMP-9 was lower in CSCR patients than controls (47.2 ± 40.7 vs 74.1 ± 42.6, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.002). A ROC curve showed that for LCN2 serum levels, the 80-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 80.3% sensitivity and 75.8% specificity, and for NGAL/MMP-9 serum levels, a 38-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 69.6% sensitivity and 80.3% specificity. In both acute and chronic CSCR, low serum LCN2 and NGAL/MMP-9, provide a biological link between the two CSCR forms, and potential susceptibility to oxidative stress and innate immune dysregulation in CSCR.
