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Journal of Pediatric Ophthalmology and... 2003
Topics: Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 12580264
DOI: 10.3928/0191-3913-20030101-04 -
Medical Science Monitor : International... Dec 2008Retinoblastoma (Rb) is the most common primary malignant intraocular tumour in childhood. The "two hit" theory, formulated by Knudson in 1971 to explain the variegated... (Review)
Review
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and more recent biological and genetic evidences, show that the "two hit" theory represents a rather simplistic, outdated, and unreliable model to explain tumour development and clinical evolution of retinoblastoma.
Topics: Age Factors; Humans; Infant; Mutation; Retinoblastoma
PubMed: 19043380
DOI: No ID Found -
Indian Journal of Ophthalmology Jun 2024Retinoblastoma is the most common pediatric ocular malignancy. It is triggered by a biallelic mutation in the RB1 gene or MYCN oncogene amplification. Retinoblastomas... (Review)
Review
Retinoblastoma is the most common pediatric ocular malignancy. It is triggered by a biallelic mutation in the RB1 gene or MYCN oncogene amplification. Retinoblastomas can be unilateral (60%-70%) or bilateral (30%-40%); bilateral tumors are always heritable and present at an earlier age as compared to unilateral ones (18-24 months vs. 36 months in India). High prevalence rates, delayed presentation, and inaccessibility to healthcare lead to worse outcomes in developing countries. The past few decades have seen a paradigm change in the treatment of retinoblastomas, shifting from enucleation and external beam radiotherapy to less aggressive modalities for eye salvage. Multimodality treatment is now the standard of care and includes intraarterial or intravenous chemotherapy along with focal consolidation therapies such as transpupillary thermotherapy, cryotherapy, and laser photocoagulation. Intravitreal and intracameral chemotherapy can help in controlling intraocular seeds. Advanced extraocular or metastatic tumors still have a poor prognosis. Genetic testing, counseling, and screening of at-risk family members must be incorporated as essential parts of management. A better understanding of the genetics and molecular basis of retinoblastoma has opened up the path for potential targeted therapy in the future. Novel recent advances such as liquid biopsy, prenatal diagnosis, prognostic biomarkers, tylectomy, and chemoplaque point to promising future directions.
Topics: Humans; Retinoblastoma; Retinal Neoplasms; Global Health; Combined Modality Therapy
PubMed: 38804799
DOI: 10.4103/IJO.IJO_2414_23 -
Seminars in Cancer Biology Apr 1995The retinoblastoma tumor suppressor gene is inactivated in retinoblastomas and a variety of other tumor types. In addition, it is one of several cellular proteins... (Review)
Review
The retinoblastoma tumor suppressor gene is inactivated in retinoblastomas and a variety of other tumor types. In addition, it is one of several cellular proteins targeted by the transforming proteins of the small DNA tumor viruses. At least two other cellular proteins that are targeted by the viral transforming proteins are structurally and functionally related to the protein encoded by the retinoblastoma tumor suppressor gene. Recent data has described a complex series of interactions with cyclins, kinases and transcription factors. It is presumably through these interactions that the retinoblastoma-related proteins exert their effects on cellular proliferation.
Topics: Adenovirus E1A Proteins; Animals; Cell Differentiation; Cell Division; Cyclins; Genes, Retinoblastoma; Humans; Mice; Nuclear Proteins; Phosphoproteins; Proteins; Retinoblastoma; Retinoblastoma Protein; Retinoblastoma-Like Protein p107; Retinoblastoma-Like Protein p130; Transcription, Genetic
PubMed: 7647310
DOI: 10.1006/scbi.1995.0011 -
Expert Reviews in Molecular Medicine Jan 2003Retinoblastoma (Rb) is the most common primary ocular malignancy of children and is caused by a mutation in the gene RB1. Approximately 40% of cases are associated with... (Review)
Review
Retinoblastoma (Rb) is the most common primary ocular malignancy of children and is caused by a mutation in the gene RB1. Approximately 40% of cases are associated with one or more constitutional mutations, and are therefore heritable, whereas the other 60% are sporadic. Rb is exclusively found in young children. In some cases, Rb tumours metastasise to extraocular organs including bone, lung and brain. Although there is no effective treatment for metastatic disease, non-metastatic cases can be cured by removal of the eye(enucleation). Newer treatment strategies emphasise salvaging the affected eye whenever possible. Animal models of Rb have been developed with xenograft and transgenic techniques. Each model has both strengths and weaknesses for exploring the mechanisms of disease development and progression and the efficacy of new treatment strategies.
Topics: Animals; Child; Disease Models, Animal; Eye; Eye Enucleation; Humans; Organ Transplantation; Retinoblastoma
PubMed: 14987394
DOI: 10.1017/S1462399403005520 -
Asia-Pacific Journal of Ophthalmology... 2024Retinoblastoma, the primary ocular malignancy in pediatric patients, poses a substantial threat to mortality without prompt and effective management. The prognosis for... (Review)
Review
Retinoblastoma, the primary ocular malignancy in pediatric patients, poses a substantial threat to mortality without prompt and effective management. The prognosis for survival and preservation of visual acuity hinges upon the disease severity at the time of initial diagnosis. Notably, retinoblastoma has played a crucial role in unraveling the genetic foundations of oncogenesis. The process of tumorigenesis commonly begins with the occurrence of biallelic mutation in the RB1 tumor suppressor gene, which is then followed by a cascade of genetic and epigenetic alterations that correspond to the clinical stage and pathological features of the tumor. The RB1 gene, recognized as a tumor suppressor, encodes the retinoblastoma protein, which plays a vital role in governing cellular replication through interactions with E2F transcription factors and chromatin remodeling proteins. The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.
Topics: Retinoblastoma; Humans; Retinal Neoplasms; Disease Management
PubMed: 38615905
DOI: 10.1016/j.apjo.2024.100058 -
Critical Reviews in Oncogenesis 2015Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor... (Review)
Review
Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor susceptibility gene (RB1). Whole-genome sequencing has made it possible to identify secondary genetic lesions following RB1 inactivation. One of the major discoveries from retinoblastoma sequencing studies is that some retinoblastoma tumors have stable genomes. Subsequent epigenetic studies showed that changes in the epigenome contribute to the rapid progression of retinoblastoma following RB1 gene inactivation. In addition, gene amplification and elevated expression of p53 antagonists, MDM2 and MDM4, may also play an important role in retinoblastoma tumorigenesis. The knowledge gained from these recent molecular, cellular, genomic, and epigenomic analyses are now being integrated to identify new therapeutic approaches that can help save lives and vision in children with retinoblastoma, with fewer long-term side effects.
Topics: Animals; Child; Epigenomics; Gene Amplification; Genetic Therapy; Humans; Retinoblastoma; Retinoblastoma Protein
PubMed: 26349417
DOI: 10.1615/critrevoncog.2015013711 -
Clinical & Translational Oncology :... May 2005
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Ophthalmic Paediatrics and Genetics Dec 1992Children diagnosed with retinoblastoma in the first year of life present with differences in laterality, stage, signs, symptoms, and respond differently to treatments... (Review)
Review
Children diagnosed with retinoblastoma in the first year of life present with differences in laterality, stage, signs, symptoms, and respond differently to treatments when compared to older children. Of those children diagnosed in the first year of life (between 1958 and 1983 inclusive), 280 were bilateral and 121 were unilateral, the most common stage of diagnosis (for unilateral and bilateral) was Group V, and children were affected equally by sex. Children examined in the first three months of life were more often seen because of a positive family history of retinoblastoma, rather than leukocoria. Children who were treated in the first year of life frequently develop second nonocular tumors because they harbor the germinal mutation and receive radiation.
Topics: Diagnosis, Differential; Eye Neoplasms; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Neoplasms, Second Primary; Retinoblastoma; Survival Rate
PubMed: 1488219
DOI: 10.3109/13816819209105167 -
International Ophthalmology Clinics 2011
Review
Topics: Combined Modality Therapy; Diagnosis, Differential; Humans; Retinal Neoplasms; Retinoblastoma
PubMed: 21139478
DOI: 10.1097/IIO.0b013e3182010f29