01 December 2008
The retinoblastoma paradigm revisited
Domenico Mastrangelo, Sonia De Francesco, Aldo Di Leonardo, Laura Lentini, Theodora HadjistilianouMed Sci Monit 2008; 14(12): RA231-240 :: ID: 869470
Abstract
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 and Method
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and more recent biological and genetic evidences, show that the "two hit" theory represents a rather simplistic, outdated, and unreliable model to explain tumour development and clinical evolution of retinoblastoma.
Keywords: Retinoblastoma - pathology, Mutation
Editorial
01 January 2023 : Editorial
Editorial: Current Status of Two Adjuvanted Malaria Vaccines and the World Health Organization (WHO) Strategy to Eradicate Malaria by 2030DOI: 10.12659/MSM.939357
Med Sci Monit 2023; 29:e939357
SARS-CoV-2/COVID-19
26 January 2023 : Editorial
Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global SpreadMed Sci Monit In Press; DOI: 10.12659/MSM.939580
19 January 2023 : Clinical Research
Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...Med Sci Monit In Press; DOI: 10.12659/MSM.938892
19 January 2023 : Clinical Research
Determining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical Research
Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...Med Sci Monit 2022; 28:e938926
In Press
30 Jan 2023 : Clinical Research
Splenic Artery Steal Syndrome in Patients with Liver Cirrhosis: A Retrospective Clinical StudyMed Sci Monit In Press; DOI: 10.12659/MSM.938998
27 Jan 2023 : Database Analysis
Association Between Neutrophil-Lymphocyte Ratio and All-Cause Mortality in Critically Ill Patients with Chr...Med Sci Monit In Press; DOI: 10.12659/MSM.938554
27 Jan 2023 : Clinical Research
Proposal for a Simple Equation for Limb Muscle Weight CalculationMed Sci Monit In Press; DOI: 10.12659/MSM.938606
26 Jan 2023 : Editorial
Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global SpreadMed Sci Monit In Press; DOI: 10.12659/MSM.939580
Most Viewed Current Articles
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952