Genetics of Retinoblastoma and Genetic Counseling
Retinoblastoma was the first cancer to be described as a genetic disease. The progression of a normal retinal cell to the eventual malignant tumor involves a step-wise accumulation of molecular genetic alterations, which correlate with clinical stage and pathology of the tumor. This chapter gives an overview of the current state of knowledge of retinoblastoma genetics and its implications for genetic counseling.
KeywordsGenetic Counseling Retinoblastoma Tumor Human Retinoblastoma Retinoblastoma Cell Line Retinoblastoma Patient
retinoblastoma that affects both eyes.
new mutation, arising sporadically in a germ cell of the proband’s parent or in early stages of embryogenesis of the proband.
the phenotypic heterogeneity in the presentation of the disease.
the RB1 allele that resulted in retinoblastoma was transmitted from a parent; children with familial retinoblastoma are constitutionally heterozygous for RB1 mutant alleles.
offspring of probands with heritable retinoblastoma are at 50% risk to inherit the mutant allele.
no family history of retinoblastoma; may or may not have a constitutional RB1 mutant allele.
the RB1 mutation occurred early in development, affecting only a subset of constitutional cells.
two or more retinoblastoma tumors affecting one eye.
the frequency at which a genotype (mutation) is expressed at the phenotypic level.
the first patient in a family to be diagnosed with retinoblastoma.
retinoblastoma develops in both eyes (or only one eye) in addition to pinealoblastoma or a primitive neuroectodermal brain tumor.
a single retinoblastoma tumor in one eye.
retinoblastoma that affects one eye.
- Dimaras H (2007) The molecular progression from retina through retinoma to retinoblastoma and the role of the p75NTR neurotrophin receptor, Department of Molecular and Medical Genetics. University of Toronto, Toronto, p 158Google Scholar
- Dimaras H et al (2008) Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma. Hom Mol Genet 17(10):1363-1372Google Scholar
- Flexner S (1891) A peculiar glioma (neuroepithelioma?) of the retina. Johns Hopkins Hosp Bull 2:115Google Scholar
- Lohmann DR, Gallie BL (2007) GENE reviews: retinoblastoma http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=retinoblastoma
- Lohmann D, Scheffer H, Gallie BL (2002) Best practice guidelines for molecular analysis of retinoblastoma. European Molecular Genetics Quality Network (EMQN)Google Scholar
- Marchong MN (2007) Identification of CDH11 as a candidate tumor suppressor in retinoblastoma and characterization of its role in retina and retinoblastoma, Department of Medical Biophysics. University of Toronto, TorontoGoogle Scholar
- Orlic M (2007) Identification of the 6p22 Oncogene in Retinoblastoma, in Molecular and Medical Genetics. University of Toronto, TorontoGoogle Scholar
- Retinoblastoma Solutions Test Sensitivity (2007) Available at: http://www.retinoblastomasolutions.org/testsent.html. Accessed 24 Oct 2007
- Zhang K et al. (2008) Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression. Hum Mutat. 29(4):475-484Google Scholar