Retinoblastoma epidemiology: Does the evidence matter?

Abstract 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been proposed that retinoblastoma is ‘caused’ by two sequential mutations affecting the RB1 gene, but this is a rather outdated view of cancer aetiology that does not take into account a large amount of new acquisitions such as chromosomal and epigenetic alterations.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 r...

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Bibliographic Details
Published in:European journal of cancer (1990) 2007-07, Vol.43 (10), p.1596-1603
Main Authors: Mastrangelo, D, De Francesco, S, Di Leonardo, A, Lentini, L, Hadjistilianou, T
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age Distribution
Age of Onset
Aneuploidy
Biological and medical sciences
Child
Child, Preschool
Chromosome instability
Epigenetic
Germ-Line Mutation - genetics
Hematology, Oncology and Palliative Medicine
Humans
Infant
Medical sciences
Microsatellite instability
Middle Aged
Pedigree
Pharmacology. Drug treatments
Retinal Neoplasms - epidemiology
Retinal Neoplasms - genetics
Retinoblastoma
Retinoblastoma - epidemiology
Retinoblastoma - genetics
Tumors
Two hit theory
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Summary:Abstract 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been proposed that retinoblastoma is ‘caused’ by two sequential mutations affecting the RB1 gene, but this is a rather outdated view of cancer aetiology that does not take into account a large amount of new acquisitions such as chromosomal and epigenetic alterations.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.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2007.04.019