Retinoblastoma (Rb) is the most common eye cancer in children and it can be inherited. Rb is quite rare and originators from the neural retina with a significant genetic component in etiology, which occurs in approxim...Retinoblastoma (Rb) is the most common eye cancer in children and it can be inherited. Rb is quite rare and originators from the neural retina with a significant genetic component in etiology, which occurs in approximately 1 in every 20 0000 births. In children with the heritable genetic form of Rb, there is a mutation on chromosome 13, called the retinoblastoma 1 (Rb1) gene. Early diagnosis and intervention is critical to the successful treatment of the Rb. The Rb1 gene is the first cloned tumor suppressor gene. As a negative regulator of the cell cycle, Rb1 gene could maintain a balance between cell growth and development through binding to transcription factors and regulating the expression of genes involved in cell proliferation and differentiation. Thus, it is involved in cell cycle, cell senescence, growth arrest, apoptosis and differentiation. We summarized the recent advances on the epidemiology and Rb1 gene of Rb in this review.展开更多
Retinoblastoma (Rb) was reported firstly by Benedict is the commonest pediatric intraocular malignant tumor in children younger than 5 years of age. The study was conducted to detect the RB-1 gene for prognostic evalu...Retinoblastoma (Rb) was reported firstly by Benedict is the commonest pediatric intraocular malignant tumor in children younger than 5 years of age. The study was conducted to detect the RB-1 gene for prognostic evaluation in retinoblastoma and to see the frequency of RB-1 gene in our population. This was a retrospective descriptive analytical study. Five years biopsies (January, 2006 to December 2011) of the retinoblastoma, from the Pathology department, was retrieved to see optic nerve involvement in all the retrieved specimens. The study was taken to see the mutation of RB1 gene by immunohistochemistry and PCR. The study plan was approved from Institutional Review Board (IRB) of the University. All the cases showed positivity of abnormal Rb-1 gene proteins expression by Immunohistochemistry staining. On PCR, 51/52 (98%) tumors expressed gene mutation as compared to 100% expression shown by IHC. Out of these, 28/51 (55%) cases showed ONI and ODI with positivity for mutated RB gene. A positive association was seen among RB gene mutation with ONI and ODI (p = 0.05). There were 33/51 (65%) cases who did not show any EOE but showed PCR positivity for RB gene mutation. While there were 18/51 (35%) cases who showed EOE and positivity of PCR for Rb-1 gene mutation and a positive association was seen with EOE and gene mutation (p = 0.005). The most common sequence of mutation was on 13 with 33 cases for double mutation, 12 cases for single and 6 patients for triple pattern of mutation. Most of the double and triple sequences of mutations were associated with ONI, ODI and EOE. We concluded that mutation of RB-1 gene is responsible in causation of the tumors with a positive association with tumor size and tumor extension (optic nerve, and extraocular extension), and mutation affects patients with all ages, both gender and unilateral and bilateral tumors.展开更多
·AIM: To collect and present updated evidence about epidemiological aspects of retinoblastoma(Rb) in the world.·METHODS: A comprehensive search without the time and language restrictions was conducted in int...·AIM: To collect and present updated evidence about epidemiological aspects of retinoblastoma(Rb) in the world.·METHODS: A comprehensive search without the time and language restrictions was conducted in international databases, including MEDLINE, Scopus, Web of Science, and Pub Med. The search keywords were “retinoblastoma” OR “retinal Neuroblastoma” OR “retinal glioma” OR “retinoblastoma eye cancer” OR “retinal glioblastoma”.·RESULTS: The worldwide incidence of Rb is 1 in 16 000-28 000 live births, but was higher in developing compared to developed countries. Several attempts for improving early detection and treatment had increased the Rb survival rate from 5% to 90% in developed countries over the past decade, but its survival was lower in developing countries(about 40% in low-income countries) and the majority of mortalities occurred in developing countries. The etiology of Rb could be viewed as genetics in the heritable form and environmental and lifestyle factors in the sporadic form. Some environmental risk factors such as in vitro fertilization;insect sprays;father’s occupational exposure to oil mists in metal working, and poor living conditions might play a role in the occurrence of the disease. Although ethnicity might affect Rb incidence, sex has no documented effect and the best treatment approaches were now ophthalmic artery chemosurgery and intravitreal chemotherapy.·CONCLUSION: Determining the role of genetics and environmental factors helps to accurately predict the prognosis and identify the mechanism of the disease, which can reduce the risk of tumor development.展开更多
In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with E2F-2.Out of 956 SNPs,we investigated 12 ...In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with E2F-2.Out of 956 SNPs,we investigated 12 nsSNPs in coding region in which three of them (SNPids rs3092895,rs3092903 and rs3092905) are commonly found to be damaged by I-Mutant 2.0,SIFT and PolyPhen programs.With this effort,we modeled the mutant pRB proteins based on these deleterious nsSNPs.From a comparison of total energy,stabilizing residues and RMSD of these three mutant proteins with native pRB protein,we identified that the major mutation is from Glutamic acid to Glycine at the residue position of 746 of pRB.Further,we compared the binding efficiency of both native and mutant pRB (E746G) with E2F-2.We found that mutant pRB has less binding affinity with E2F-2 as compared to native type.This is due to sixteen hydrogen bonding and two salt bridges that exist between native type and E2F-2,whereas mutant type makes only thirteen hydrogen bonds and one salt bridge with E2F-2.Based on our investigation,we propose that the SNP with an id rs3092905 could be the most deleterious nsSNP in RB1 gene causing retinoblastoma.展开更多
The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of ...The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of the exogenous active(ΔB/X andΔр34)or inactive(ΔS/N)forms of RB into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous RB,despite being G-418 resistant.However,the consequences of the transient production of exogenous RB had different effects on the cell fate.TheΔB/X andΔр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation(AD).On the contrary,theΔS/N cells transfected with inactive RB mutant were insensitive to induction of AD associated with abolishing of expression of the PPARγ2.Additionally,the PPARγ2 promoter in undifferentiatedΔS/N cells was hypermethylated,but all except−60 position CpG became mostly demethylated after cells exposure to AD.We conclude that while transient expression of inactive exogenous RB induces long term epigenetic alterations that prevent adipogenesis,production of active exogenous RBs results in an AD-promoting epigenetic state.These results indicate that pRb is involved in the establishment of hereditary epigenetic memory at least by creating a methylation pattern of PPARγ2.展开更多
文摘Retinoblastoma (Rb) is the most common eye cancer in children and it can be inherited. Rb is quite rare and originators from the neural retina with a significant genetic component in etiology, which occurs in approximately 1 in every 20 0000 births. In children with the heritable genetic form of Rb, there is a mutation on chromosome 13, called the retinoblastoma 1 (Rb1) gene. Early diagnosis and intervention is critical to the successful treatment of the Rb. The Rb1 gene is the first cloned tumor suppressor gene. As a negative regulator of the cell cycle, Rb1 gene could maintain a balance between cell growth and development through binding to transcription factors and regulating the expression of genes involved in cell proliferation and differentiation. Thus, it is involved in cell cycle, cell senescence, growth arrest, apoptosis and differentiation. We summarized the recent advances on the epidemiology and Rb1 gene of Rb in this review.
文摘Retinoblastoma (Rb) was reported firstly by Benedict is the commonest pediatric intraocular malignant tumor in children younger than 5 years of age. The study was conducted to detect the RB-1 gene for prognostic evaluation in retinoblastoma and to see the frequency of RB-1 gene in our population. This was a retrospective descriptive analytical study. Five years biopsies (January, 2006 to December 2011) of the retinoblastoma, from the Pathology department, was retrieved to see optic nerve involvement in all the retrieved specimens. The study was taken to see the mutation of RB1 gene by immunohistochemistry and PCR. The study plan was approved from Institutional Review Board (IRB) of the University. All the cases showed positivity of abnormal Rb-1 gene proteins expression by Immunohistochemistry staining. On PCR, 51/52 (98%) tumors expressed gene mutation as compared to 100% expression shown by IHC. Out of these, 28/51 (55%) cases showed ONI and ODI with positivity for mutated RB gene. A positive association was seen among RB gene mutation with ONI and ODI (p = 0.05). There were 33/51 (65%) cases who did not show any EOE but showed PCR positivity for RB gene mutation. While there were 18/51 (35%) cases who showed EOE and positivity of PCR for Rb-1 gene mutation and a positive association was seen with EOE and gene mutation (p = 0.005). The most common sequence of mutation was on 13 with 33 cases for double mutation, 12 cases for single and 6 patients for triple pattern of mutation. Most of the double and triple sequences of mutations were associated with ONI, ODI and EOE. We concluded that mutation of RB-1 gene is responsible in causation of the tumors with a positive association with tumor size and tumor extension (optic nerve, and extraocular extension), and mutation affects patients with all ages, both gender and unilateral and bilateral tumors.
文摘·AIM: To collect and present updated evidence about epidemiological aspects of retinoblastoma(Rb) in the world.·METHODS: A comprehensive search without the time and language restrictions was conducted in international databases, including MEDLINE, Scopus, Web of Science, and Pub Med. The search keywords were “retinoblastoma” OR “retinal Neuroblastoma” OR “retinal glioma” OR “retinoblastoma eye cancer” OR “retinal glioblastoma”.·RESULTS: The worldwide incidence of Rb is 1 in 16 000-28 000 live births, but was higher in developing compared to developed countries. Several attempts for improving early detection and treatment had increased the Rb survival rate from 5% to 90% in developed countries over the past decade, but its survival was lower in developing countries(about 40% in low-income countries) and the majority of mortalities occurred in developing countries. The etiology of Rb could be viewed as genetics in the heritable form and environmental and lifestyle factors in the sporadic form. Some environmental risk factors such as in vitro fertilization;insect sprays;father’s occupational exposure to oil mists in metal working, and poor living conditions might play a role in the occurrence of the disease. Although ethnicity might affect Rb incidence, sex has no documented effect and the best treatment approaches were now ophthalmic artery chemosurgery and intravitreal chemotherapy.·CONCLUSION: Determining the role of genetics and environmental factors helps to accurately predict the prognosis and identify the mechanism of the disease, which can reduce the risk of tumor development.
文摘In this study,we identified the most deleterious nsSNP in RB1 gene through structural and functional properties of its protein (pRB) and investigated its binding affinity with E2F-2.Out of 956 SNPs,we investigated 12 nsSNPs in coding region in which three of them (SNPids rs3092895,rs3092903 and rs3092905) are commonly found to be damaged by I-Mutant 2.0,SIFT and PolyPhen programs.With this effort,we modeled the mutant pRB proteins based on these deleterious nsSNPs.From a comparison of total energy,stabilizing residues and RMSD of these three mutant proteins with native pRB protein,we identified that the major mutation is from Glutamic acid to Glycine at the residue position of 746 of pRB.Further,we compared the binding efficiency of both native and mutant pRB (E746G) with E2F-2.We found that mutant pRB has less binding affinity with E2F-2 as compared to native type.This is due to sixteen hydrogen bonding and two salt bridges that exist between native type and E2F-2,whereas mutant type makes only thirteen hydrogen bonds and one salt bridge with E2F-2.Based on our investigation,we propose that the SNP with an id rs3092905 could be the most deleterious nsSNP in RB1 gene causing retinoblastoma.
文摘The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of the exogenous active(ΔB/X andΔр34)or inactive(ΔS/N)forms of RB into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous RB,despite being G-418 resistant.However,the consequences of the transient production of exogenous RB had different effects on the cell fate.TheΔB/X andΔр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation(AD).On the contrary,theΔS/N cells transfected with inactive RB mutant were insensitive to induction of AD associated with abolishing of expression of the PPARγ2.Additionally,the PPARγ2 promoter in undifferentiatedΔS/N cells was hypermethylated,but all except−60 position CpG became mostly demethylated after cells exposure to AD.We conclude that while transient expression of inactive exogenous RB induces long term epigenetic alterations that prevent adipogenesis,production of active exogenous RBs results in an AD-promoting epigenetic state.These results indicate that pRb is involved in the establishment of hereditary epigenetic memory at least by creating a methylation pattern of PPARγ2.
