RB1
In
databases:
● Ensembl (http://www.ensembl.org/index.html):
ENSG00000139687
● HGNC (http://www.genenames.org/): 9884 or RB1
Gene locus:
13q14.2
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
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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