mercredi 25 avril 2012

Mutated genes in cancer (66) – RB1


In databases:

● Entrez ( 5925 or RB1
● Ensembl ( ENSG00000139687
● UniProt ( P06400
● GeneCards ( RB1
● HGNC ( 9884 or RB1

Gene locus:


Protein name:

Retinoblastoma 1

Protein Size:

928 amino acids; about 106 kDa

Function :

The protein encoded by RB1 was the first tumor suppressor gene identified. It is key regulator of entry into cell division. Its active, hypophosphorylated form binds transcription factor E2F1 and represses its transcription activity, leading to cell cycle arrest. RB1 recruits and targets several histone methyltransferases, leading to epigenetic transcriptional repression. RB1 also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. RB1 has many other effects on specific targets depending on the cell type.

Cancer-related alterations:

Germinal RB1 mutations are causative for hereditary predisposition to retinoblastoma (RB), which is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.
The spectrum of predisposing RB1 mutations includes large deletions (about 20%), single base substitutions (about 50%) and small length mutations (about 30%); most mutations are associated with almost complete penetrance: some rare alleles show incomplete penetrance and reduced expressivity (low penetrance retinoblastoma)

Somatic RB1 mutations: in sporadic RB, both RB1 alleles are somatically mutated. Somatic RB1 mutations are found in a variety of tumors affecting eye (about 50% of cases), urinary tract and bladder, endometrium, breast, bone (osteogenic sarcoma), lung, ovary, liver, stomach…
Deletions, insertions and point mutations are observed. There are no mutational hot spots.

References (open access):

Retinoblastoma. Lohmann DR, Gallie BL. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2000 Jul 18 [updated 2010 Jun 10].

A comprehensive, sensitive and economical approach for the detection of mutations in the RB1 gene in retinoblastoma. Parsam VL, Kannabiran C, Honavar S, Vemuganti GK, Ali MJ. J Genet. 2009 Dec;88(4):517-27.

Retinoblastoma and the genetic theory of cancer: an old paradigm trying to survive to the evidence. Mastrangelo D, Hadjistilianou T, De Francesco S, Loré C. J Cancer Epidemiol. 2009;2009:301973.

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