Retinoblastoma: from discovery to clinical management

Martínez-Sánchez, Mayra; Hernández-Monge, Jesús; Rangel, Martha; Olivares‐Illana, Vanesa

doi:10.1111/febs.16035

Cited by 17 publications

(11 citation statements)

References 92 publications

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“…Human RB protein (pRB) has a mass of 106 kDa (106,159 Da) and consists of 928 amino acids. It has been demonstrated that this protein functions in a wide network of molecular interactions [ 3 , 18 ]. The function and the structure of this protein has been extensively studied for decades; however, its many molecular functions still need investigation.…”

Section: Prb Protein Structure and Functionmentioning

confidence: 99%

“…pRB protein versatile functions are illustrated by many different protein interactions it performs. Besides E2F family members, pRB interacts with chromatin modifiers such as DNMT1, HDAC, SIRT1, the replication factor C, the DNA polymerase α, MDMX and MDM2 [ 3 ]. For example, it has been shown that MDM2 is an important regulator of the RB activity with dual roles, when in G1 phase it can bind to the RB mRNA and enhance the RB translation, while during G2 MDM2 can degrade pRB.…”

Section: Prb Protein Structure and Functionmentioning

confidence: 99%

“…Knudson’s two hit model proposed that one RB1 allele is lost or mutated in all cells and a second somatic mutagenic event affects the remaining allele in a primitive retinal cell, thus initiating tumorigenesis. More than 10 years after Knudson’s discovery, RB1 gene was the first tumor suppressor gene to be identified and cloned [ 3 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Genetics in ophthalmology: molecular blueprints of retinoblastoma

Marković,

Bukovac,

Varošanec

et al. 2023

Hum Genomics

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This review presents current knowledge on the molecular biology of retinoblastoma (RB). Retinoblastoma is an intraocular tumor with hereditary and sporadic forms. 8,000 new cases of this ocular malignancy of the developing retina are diagnosed each year worldwide. The major gene responsible for retinoblastoma is RB1, and it harbors a large spectrum of pathogenic variants. Tumorigenesis begins with mutations that cause RB1 biallelic inactivation preventing the production of functional pRB proteins. Depending on the type of mutation the penetrance of RB is different. However, in small percent of tumors additional genes may be required, such as MYCN, BCOR and CREBBP. Additionally, epigenetic changes contribute to the progression of retinoblastoma as well. Besides its role in the cell cycle, pRB plays many additional roles, it regulates the nucleosome structure, participates in apoptosis, DNA replication, cellular senescence, differentiation, DNA repair and angiogenesis. Notably, pRB has an important role as a modulator of chromatin remodeling. In recent years high-throughput techniques are becoming essential for credible biomarker identification and patient management improvement. In spite of remarkable advances in retinoblastoma therapy, primarily in high-income countries, our understanding of retinoblastoma and its specific genetics still needs further clarification in order to predict the course of this disease and improve therapy. One such approach is the tumor free DNA that can be obtained from the anterior segment of the eye and be useful in diagnostics and prognostics.

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Section: Prb Protein Structure and Functionmentioning

confidence: 99%

Section: Prb Protein Structure and Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetics in ophthalmology: molecular blueprints of retinoblastoma

Marković,

Bukovac,

Varošanec

et al. 2023

Hum Genomics

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“…In children, retinoblastoma (Rb) is a relatively common human genetic malignant ocular tumour (1)(2)(3)(4). It has the characteristics of high incidence, and low survival rate usually occurs in children under 3 years old and can affect one or both two eyes and seriously affect the health of children (5)(6)(7). Rb can be divided into two genetic modes: germline inheritance and non-germline inheritance (8).…”

Section: Introductionmentioning

confidence: 99%

The clinical diagnostic value of plasma miR-592 and miR-217-3p levels in retinoblastoma

Huang

Luo

et al. 2022

J Med Biochemistry

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目的：研究血浆miR-592和miR-217-3p在视网膜母细胞瘤（Rb）中的异常表达，探讨其表达水平对Rb的临床诊断价值。方法：选取2018年1月至2019年1月到南昌市洪都中医院就诊的100例Rb患者为Rb组，同期来体检中心就诊的100例健康患者为对照组. 采用实时荧光定量PCR（qRT-PCR）检测所有受试者血浆miR-592和miR-217-3p的表达水平；分析血浆miR-592和miR-217-3p水平与Rb临床病理特征的关系；Pearson 相关分析评估了血浆 miR-592 和 miR-217-3p 水平与总生存率之间的关系。结果： Rb组血浆miR-592和miR-217-3p水平显着高于对照组（p < 0.0001），且miR-592的表达与家族遗传史显着相关（p＜ 0.0001)、肿瘤偏倚( p =0.0081)、淋巴结转移( p =0.0048)和病理分级( p =0.0025)，miR-217-3p的表达与家族遗传史显着相关( p＜0.0001)，视神经浸润（p＜0.0001）、淋巴结转移（p = 0.0090）、病理分级（p＜0.0001)。miR-592和miR-217-3p的高表达是Rb更严重的病理表现，随着miR-592（r=-0.2276，p =0.0052）和miR的升高，患者的总生存期显着缩短-217-3p 水平（r=-0.6461，p＜0.0001）。结论： miR-592和miR-217-3p在Rb患者血浆中高表达，其升高的水平呈现Rb严重的病理表现和缩短的总生存期，有望成为Rb临床诊断的生物标志物。

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“…Research into novel biomarkers is an effective way to improve the probability of satisfactory outcomes, including the prognosis and quality of life in patients with retinoblastoma. Although new molecular biomarkers for retinoblastoma have been revealed in recent years [7][8][9][10][11], they are still in the experimental stage and have not been approved for clinical use [12]. Currently, there is no gold standard biomarker for the diagnosis and treatment of retinoblastoma.…”

Section: Introductionmentioning

confidence: 99%

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma

Shi

Zhu

et al. 2021

Bioengineered

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Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub genes, including benzimidazoles 1 (BUB1), cyclin dependent kinase 1 (CDK1), centromere protein E (CENPE), kinesin family member 20A (KIF20A), PDZ binding kinase (PBK), and targeting protein for xklp2 (TPX2). Drug sensitivity analysis showed that nelarabine was positively correlated with five hub genes. All six genes were expressed differently in six immune subtypes and were positively correlated with stemness indices in most human cancer types. Since CENPE is the least known hub gene in retinoblastoma, we further analyzed the potential noncoding RNAs and transcription factors that regulate CENPE and built interaction networks of competing endogenous RNA and transcription factors. Immune cell infiltration, especially by plasma and B cells, was enhanced in samples with high CENPE expression. Pan-cancer analysis illustrated that CENPE was highly expressed in a wide range of human tumors. In vitro validation revealed that CENPE was significantly upregulated at both the mRNA and protein levels in retinoblastoma cells. In conclusion, CENPE, along with other hub genes, could serve as a potential biomarker and intervention target for retinoblastoma.

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Retinoblastoma: from discovery to clinical management

Cited by 17 publications

References 92 publications

Genetics in ophthalmology: molecular blueprints of retinoblastoma

Genetics in ophthalmology: molecular blueprints of retinoblastoma

The clinical diagnostic value of plasma miR-592 and miR-217-3p levels in retinoblastoma

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma

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