6533b7d6fe1ef96bd1265b7f
RESEARCH PRODUCT
Retinoblastoma epidemiology: Does the evidence matter?
Domenico MastrangeloTheodora HadjistilianouLaura LentiniA. Di LeonardoS De Francescosubject
AdultCancer ResearchAdolescentRetinal NeoplasmsRetinoblastoma Aneuploidy Two hit theoryDiseaseBiologyAge DistributionChromosome instabilitymedicineHumansEpigeneticsAge of OnsetChildGerm-Line MutationGeneticsRetinoblastomaRetinoblastomaMicrosatellite instabilityCancerInfantMiddle Agedmedicine.diseasePedigreeSettore BIO/18 - GeneticaOncologyChild PreschoolDNA methylationDNA mismatch repairdescription
It has been proposed that retinoblastoma is 'caused' by two sequential mutations affecting the RB1 gene, but this is a rather outdated view of cancer aetiology that does not take into account a large amount of new acquisitions such as chromosomal and epigenetic alterations. Retinoblastoma remains probably the only cancer in which the rather simplistic 'two hit' mutational model is still considered of value, although cancer is known to be associated with genomic and microsatellite instability, defects of the DNA mismatch repair system, alterations of DNA methylation and hystone acethylation/deacethylation, and aneuploidy. Moreover, as it is shown herein, the predictions made by the 'two hit' model, are not fulfilled by the clinical and epidemiological data reported so far. Moreover, while the role of mutational events in cancer has been largely questioned in the more recent literature, no serious effort has been done to investigate the role of epigenetic alterations and aneuploidy in retinoblastoma. Through the analysis of the specialised literature and a set of original epidemiological and biological data concerning retinoblastoma, the authors illustrate the evidences arguing against the 'two hit' hypothesis and propose that epigenetic factors and aneuploidy play central roles in the disease.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-01-01 |