Retinoblastoma

Identity

Atlas_Id	10031
Genes implicated in	RB1
Inheritance	predisposition to retinoblastoma is transmitted as an autosomal dominant trait; it is caused by mutations in the RB1 gene; penetrance and expressivity depend on the nature of the predisposing mutational change; there is also a non-hereditary form of retinoblastoma (mostly in children with isolated unilateral retinoblastoma) that is caused by RB1-mutations confined to somatic cells

Clinics

Phenotype and clinics	retinoblastoma in early childhood: white reflexes in one or both eyes or strabismus usually are the first signs indicating this malignant eye tumour; in most children with the hereditary retinoblastoma, both eyes are affected by multiple tumour foci (bilateral multifocal retinoblastoma) adults (most often relatives of patients with retinoblastoma) may show retinal scars indicating regressed (non-progressive tumours). in addition to retinoblastoma, children with cytogenetic deletions involving 13q14 may show developmental delay and dysmorphic signs.
Neoplastic risk	early childhood: formation of retinoblastomas (see genotype-phenotype correlation) adolescence and adulthood: tumours outside the eye (second primary neoplasms): osteosarcoma, melanoma, brain tumours (pinealoma in particular some patients also show multiple benign tumours of adipose tissue (lipoma).
Treatment	retinoblastomas can be cured by (depending on size and location): local therapy (photocoagulation, cryotherapy, radiation), combined systemic and local therapy, or enucleation of the eye; surveillance : following the diagnosis of retinoblastoma, repeated examinations under general anesthesia are required for early diagnosis of new tumour foci; up to now, no screening for second primary neoplasms.
Prognosis	most often, treatment of retinoblastoma is very effective and, therefore, death from retinoblastoma is rare; however, life span in patients that develop second primary neoplasms is reduced (cumulative mortality at age 40: 6.4% in bilateral patients without radiotherapy, 1.5% in patients with unilateral retinoblastoma).

Genes involved and Proteins

Gene Name	RB1 (retinoblastoma susceptibility gene)
Location	13q14

DNA/RNA
Description	180 kb genomic DNA containing 27 exons
Transcription	4.7 kb mRNA with 2.7 kb open reading frame

Protein
Description	928 aa nuclear phosphoprotein
Localisation	nucleus
Function	involved in cell cycle regulation

Mutations

Note

mutations predisposing to retinoblastoma are one allele mutations; in retinoblastoma, both copies of the RB1 gene are mutated (two-step inactivation mechanism typical of tumor suppressor genes). nature and localization of individual mutations are heterogeneous regarding their nature : 20% deletions larger 1kb; 30% small deletions or insertions; 45% point mutations. and location : mutations have been found in 25 of the 27 coding exons and in promoter elements. Genotype-phenotype correlation : most mutant RB1-alleles show premature termination codons; typically, these mutant alleles are associated with almost complete penetrance (>95%) and high expressivity (more than 6 individual retinoblastoma foci per individual and, therefore, most often involvement of both eyes); some rare mutant alleles that code for proteins with retention of parts of the functions of the wild-type prote in or that result in diminished amounts of wild-type transcript are associated with incomplete penetrance (<75%) and low expressivity (mean of less than 2 tumor foci).

Bibliography

Presenting signs of retinoblastoma.

Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd NW 3rd

The Journal of pediatrics. 1998 ; 132 (3 Pt 1) : 505-508.

PMID 9544909

Molecular etiology of low-penetrance retinoblastoma in two pedigrees.

Dryja TP, Rapaport J, McGee TL, Nork TM, Schwartz TL

American journal of human genetics. 1993 ; 52 (6) : 1122-1128.

PMID 8099255

Mortality from second tumors among long-term survivors of retinoblastoma.

Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, Seddon J, Tarbell N, Boice JD Jr

Journal of the National Cancer Institute. 1993 ; 85 (14) : 1121-1128.

PMID 8320741

Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism.

Fleischman RA, Gallardo T, Mi X

The Journal of investigative dermatology. 1996 ; 107 (5) : 703-706.

PMID 8875953

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma.

Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP

Nature. 1986 ; 323 (6089) : 643-646.

PMID 2877398

Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy.

Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, Ling V, Chan HS

Archives of ophthalmology. 1996 ; 114 (11) : 1321-1328.

PMID 8906022

Retinoma: spontaneous regression of retinoblastoma or benign manifestation of the mutation?

Gallie BL, Ellsworth RM, Abramson DH, Phillips RA

British journal of cancer. 1982 ; 45 (4) : 513-521.

PMID 7073943

A simplified scheme for genetic counseling in retinoblastoma.

Musarella MA, Gallie BL

Journal of pediatric ophthalmology and strabismus. 1987 ; 24 (3) : 124-125.

PMID 3598831

Oncogenic germ-line mutations in Sp1 and ATF sites in the human retinoblastoma gene.

Sakai T, Ohtani N, McGee TL, Robbins PD, Dryja TP

Nature. 1991 ; 353 (6339) : 83-86.

PMID 1881452

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

Sippel KC, Fraioli RE, Smith GD, Schalkoff ME, Sutherland J, Gallie BL, Dryja TP

American journal of human genetics. 1998 ; 62 (3) : 610-619.

PMID 9497263

Complete genomic sequence of the human retinoblastoma susceptibility gene.

Toguchida J, McGee TL, Paterson JC, Eagle JR, Tucker S, Yandell DW, Dryja TP

Genomics. 1993 ; 17 (3) : 535-543.

PMID 7902321

Citation

This paper should be referenced as such :

Lohmann, DR

Retinoblastoma

Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):48-49.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Tumors/RbKprID10031.html

External links

OMIM	180200
Orphanet	Retinoblastoma
MeSH	D012175
MedGen	D012175
UMLS	C0035335
ICD-10	C69.2
HGMD	118734
Other database	Database of RB1-gene mutations

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Fri Jun 30 11:24:35 CEST 2017

For comments and suggestions or contributions, please contact us