Pediatric retinal and neuroepithelial tumors

2024-12-07   Paola Dal Cin, PhD 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)

Keywords
Retinoblastoma, retinocytoma, intraocular medulloepithelioma , RB1, NMYC

Classification

Definition

Retinoblastoma is the most common eye cancer in children and is usually caused by biallelic inactivation of the RB1 gene but can also be caused by MYCN amplification of the neuroblastoma. 1
Retinocytoma represents a rare differentiated and benign retinal, with low risk for transformation into active retinoblastoma with the accumulation of additional mutational events. 2
Intraocular medulloepithelioma is mainly sporadic with complex clinical manifestations difficult to differentiate from retinoblastoma. 3 Evaluation of systemic associations with DICER1 gene mutations must be performed. 4

Pediatric eye tumors
Retinal and neuroepithelial tumorsGenetic marker(s)
Retinocytoma Retinocytoma (retinoma) is a rare benign benign, inactive retinal tumor, typically in children, that resembles regressed or arrested retinoblastoma. There is low risk for transformation into active retinoblastoma with the accumulation of additional mutational events e.g., gains of MDM4 ,MYCN and E2F3, suggesting that it rather represents a pre-malignant lesion. 2,5 . 2% of persons with a germline RB1 mutation develop a retinocytoma. 6
Retinoblastoma Retinoblastoma is the most common intraocular malignancy in children,OMIM:180200 either heritable or ,the more common, non-heritable. 7 According to the two-hit hypothesis proposed by Knudson in 1971, the heritable forms inherited one heterogenous RB1 mutation including single base substitution, large deletions, hypermethylation of the promoter region or chromothrypsis,  8 and have a second somatic mutation resulting in uncontrolled cell priliferation. All bilateral patients have a RB1 germline mutation , which only require a second hit to initiate cancer, usually in multiple cells, in both eyes. 9 Non-heritable forms necessitate bi-allelic somatic RB1 mutation in a susceptible cell, typically presenting later in life.9 Unilateral patients (usually) have lost both RB1 wild-type alleles in a susceptible retinal cell (two hits), leading to a single, unifocal tumor. 10 Additional recurrent aberrations were detected : gains of 1q MDM4 and KIF14,2p MYCN , 6p DEK and E2F3 and loss of 16q CDH11 and RBL2 ,and also a variety of dysregulated microRNAs.11-14
A minority of unilateral retinoblastomas, instead of RB1 inactivation, have an amplification of the MYCN oncogene (28‒ 121 DNA copies) only identifiable after enucleation, typically present in early infancy 15 and with variations in common with neuroblastoma (17q gain, 11q loss). 1,16
MedulloepitheliomaDICER1 mutations can occurr intraocular medulloepithelioma sporadically or in patients with DICER1-related pleuropulmonary blastoma familial tumor predisposition syndrome. 17,18 In addition significant dysregulated miRNAs, 19 as well as KMT2D mutations 20 have been also reported. A significant genomic instability on chromosomes 1p, 4, 8, and 16p have observed in most of these tumors. 21

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1392615662024Author Correction: A MYCN-driven de-differentiation profile identifies a subgroup of aggressive retinoblastoma.Ryl T et al
2340513572021Retinocytoma/retinoma: comparative analysis of clinical features in 78 tumors and rate of transformation into retinoblastoma over 20 years.Shields CL et al
3313418192019Intraocular medulloepithelioma in children: clinicopathologic features itself hardly differentiate it from retinoblastoma.Lee J et al
4380839352023Intraocular medulloepithelioma: an unusual and challenging entity in paediatric population.Imam U et al
5191833422009Array comparative genomic hybridization in retinoma and retinoblastoma tissues.Sampieri K et al
6319975592020Unilateral retinocytoma associated with a variant in the RB1 gene.Wu S et al
7283993382017Genetics and Molecular Diagnostics in Retinoblastoma--An Update.Soliman SE et al
8152642692004Retinoblastoma: revisiting the model prototype of inherited cancer.Lohmann DR et al
9293141422019Retinoblastoma, the visible CNS tumor: A review.Dimaras H et al
10348517862021The Genetics of Unilateral Retinoblastoma Clarified.Wagner RS et al
11174372782007One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma.Corson TW et al
12268834512016Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing.García-Chequer AJ et al
13282116172017Phosphorylation of pRb: mechanism for RB pathway inactivation in MYCN-amplified retinoblastoma.Ewens KG et al
14344787402021Molecular alterations in retinoblastoma beyond RB1.Mendonça V et al
15234987192013Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies.Rushlow DE et al
16387961082024Role of MYCN in retinoblastoma: A review of current literature.Vempuluru VS et al
17257915832015Somatic DICER1 gene mutation in sporadic intraocular medulloepithelioma without pleuropulmonary blastoma syndrome.Durieux E et al
18311244832019Intraocular medulloepithelioma - A review of clinical features, DICER 1 mutation, and management.Tadepalli SH et al
19258071412015MicroRNA profiling in intraocular medulloepitheliomas.Edward DP et al
20268416982016Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas.Sahm F et al
21261833842015Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.Korshunov A et al

Citation

Paola Dal Cin, PhD

Pediatric retinal and neuroepithelial tumors

Atlas Genet Cytogenet Oncol Haematol. 2024-12-07

Online version: http://atlasgeneticsoncology.org/solid-tumor/209302/pediatric-retinal-and-neuroepithelial-tumors