Document Detail


The retinoblastoma paradigm revisited.
MedLine Citation:
PMID:  19043380     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Retinoblastoma (Rb) is the most common primary malignant intraocular tumour in childhood. The "two hit" theory, formulated by Knudson in 1971 to explain the variegated clinical expression of the disease, led to the discovery of the so called tumour suppressor genes and the identification of the Rb1 as the prototype of such genes. Mutations of the Rb1 gene are now commonly believed to be the "cause" retinoblastoma, although epidemiological, clinical, and biological evidences argue against it. MATERIAL/METHODS: The Authors have performed a systematic review of available data concerning clinical and diagnostic aspects of retinoblastoma, including molecular genetics. Meta analysis of literature data has been performed in order to validate some of the predictions made by the two hit theory. RESULTS: The following theses are discussed in detail: 1) there is no difference in the age at diagnosis between unilateral and bilateral retinoblastoma; 2) the pathogenetic mechanisms underlying familial, hereditary, and sporadic retinoblastoma are different; 3) bilateral retinoblastoma is not necessarily hereditary; 4) The real incidence of the unilateral phenotype within the familial group is disproportionately higher than that predicted by the "two hit"; 5) retinoblastoma is most probably "caused" by the combination of epigenetic factors and aneuploidy. CONCLUSIONS: Epidemiological, clinical, and more recent biological and genetic evidences, show that the "two hit" theory represents a rather simplistic, outdated, and unreliable model to explain tumour development and clinical evolution of retinoblastoma.
Authors:
Domenico Mastrangelo; Sonia De Francesco; Aldo Di Leonardo; Laura Lentini; Theodora Hadjistilianou
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Medical science monitor : international medical journal of experimental and clinical research     Volume:  14     ISSN:  1643-3750     ISO Abbreviation:  Med. Sci. Monit.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2009-02-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9609063     Medline TA:  Med Sci Monit     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  RA231-40     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology (Ocular Oncology Unit), University of Siena, Siena, Italy. mastrangelo@unisi.it
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Humans
Infant
Mutation
Retinoblastoma / diagnosis*,  genetics*,  pathology

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


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