Retinoblastoma: Revisiting the model prototype of inherited cancer

  title={Retinoblastoma: Revisiting the model prototype of inherited cancer},
  author={Dietmar R Lohmann and Brenda L. Gallie},
  journal={American Journal of Medical Genetics Part C: Seminars in Medical Genetics},
  • D. Lohmann, B. Gallie
  • Published 15 August 2004
  • Medicine
  • American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Hereditary retinoblastoma is an autosomal dominant disorder caused by mutations in the RB1 gene. Analysis of this rare condition has helped to elucidate the mechanisms underlying hereditary cancer predisposition in general. As identification of RB1 gene mutations has become a part of clinical management of patients with retinoblastoma, there is now a wealth of data. In this article, we summarize the current knowledge on the relations between the genotype and phenotypic expression. Moreover… 

Genetics of retinoblastoma

The different types of mutations are reviewed and the genotype–phenotype relationship demonstrating the complexity and the genetic diversity of retinoblastoma is analyzed, as well as future potential clinical applications and new therapeutic targets.

Molecular Genetics of RB1——The Retinoblastoma Gene

The purpose of this review is to provide a concise overview of the molecular genetics and genotype-phenotype correlations in retinoblastoma.

RETRACTED ARTICLE: Molecular biology of retinoblastoma

The history of Rb research highlights how basic research on a rare childhood cancer can have a much broader effect on a disease that affects millions of people each year worldwide.

Mutation Spectrum of RB1 Gene in Unilateral Retinoblastoma Cases from Tunisia and Correlations with Clinical Features

20% of the individuals with sporadic unilateral RB in this series carried germline mutations and indicate the importance of genetic testing all children with sporadic retinoblastoma, and help to characterize the spectrum of mutations present in the Tunisian population.

RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database

The analysis of RB1 gene mutations logged in the RBGMdb has shown relevant phenotype-genotype relationships and provided working hypothesis to ascertain mechanisms linking certain mutations to ethnicity, delayed onset of the disease and low-penetrance.

Challenges of Genetic Susceptibility Testing for Retinoblastoma

The role of genetics professionals and the challenges that clinicians face with the interpretation and complexities of germline testing for patients with RB are focused on.

Pediatric Malignancies: Retinoblastoma and Wilms’ Tumor

The clinical features and genetics of these two disorders and the implications for management, early detection and potential prevention of these disorders are reviewed.

pRb2/p130: a new candidate for retinoblastoma tumor formation

Current knowledge about the molecular mechanisms involved in retinoblastoma is analyzed, paying particular attention to the mechanisms of inactivation of the biological function of the retinOBlastoma family of proteins.

Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations

Screening of mutations in the RB1 gene can help to identify heritable Rb and contribute to clinical management and genetic counseling for affected families.



Molecular etiology of low-penetrance retinoblastoma in two pedigrees.

In one family with low-penetrance retinoblastoma, a germ-line deletion is shared by affected and unaffected, obligate carriers and RFLP analysis shows that two distant relatives have independently derived mutations.

RB1 gene mutations in retinoblastoma

Analysis of 368 reported small mutations reveals considerable heterogeneity, and a notable recurrence of transitions is observed at 13 CpG‐dinucleotides that are part of CGA codons or splice donor sites.

Two novel germline mutations of the retinoblastoma gene (RB1) that show incomplete penetrance, one splice site and one missense

DNA analysis of markers within and flanking the RB1 gene allows the identification within retinoblastoma families of healthy subjects in whom the mutation is non-penetrant and resembles true asymptomatic carriers of an RB1 germline mutation.

Multiple lipomas linked to an RB1 gene mutation in a large pedigree with low penetrance retinoblastoma

The data indicate that lipoma predisposition in hereditary retinoblastoma is not associated with specific RB1 gene mutations but is influenced by modifying factors linked to this gene.

Mechanisms of loss of heterozygosity in retinoblastoma.

To further delineate the mechanism of LOH, a total of 37 RB tumors were screened for LOH by Southern blot analysis, andeteen of 30 informative tumors from 27 patients showed LOH.

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

A comparison of constitutional and tumour genotypes from several cases indicates that tumorigenesis may result from the development of homozygosity for the mutant allele at the Rb-1 locus.

Constitutional RB1-gene mutations in patients with isolated unilateral retinoblastoma.

The results emphasize that the manifestation and transmissibility of retinoblastoma depend on the nature of the first mutation, its time in development, and the number and types of cells that are affected.

Frequency of somatic and germ-line mosaicism in retinoblastoma: implications for genetic counseling.

Genetic tests of germ-line DNA can provide valuable information that is not available through analysis of somatic (leukocyte) DNA, especially in disorders such as retinoblastoma, in which a high proportion of cases represent new mutations.

Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma

It is tentatively concluded that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinOBlastoma (RB) locus.

Incomplete penetrance of familial retinoblastoma linked to germ-line mutations that result in partial loss of RB function.

Two categories of mutant, low-penetrant RB alleles are suggested: Class 1 alleles correspond to promoter mutations, which are believed to result in reduced or deregulated levels of wild-type RB protein, whereas class 2 alleles result in mutant proteins that retain partial activity.