Genetics
Retinoblastoma
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Get access- Tumour of primitive photoreceptor cells
- Commonest ocular malignancy of childhood: 1 in 20,000
- M=F
- 40% are inherited: tumours tend to be bilateral and multicentric
- Unilateral tumour is nearly always sporadic
Hereditary cases: only 10% have a positive family history. The remainder have a new mutation in the germ cells
The hereditary pattern is autosomal dominant but at the cellular level the condition behaves in a recessive manner
Hemizygosity of the Rb locus within band 13q14 confers a predisposition (germ line mutation carrier)
- Rb locus is a member of the tumour suppressor gene class
- At least 1 active normal allele is needed to prevent uncontrolled proliferation
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Familial cases of retinoblastoma also carry risk of osteosarcoma and pinealoma (so-called trilateral disease)
- Genetics
- Knudson’s two-hit hypothesis proposed two mutational events in retinoblastoma
First mutation in the germinal cell (therefore every cell) either by inheritance of germinal mutation, or by somatic mutation
- Second mutation is somatic within an already mutated cell
Note: two somatic mutations would be needed in sporadic cases hence they are likely to be just unilateral
Examples: retinoblastoma, neurofibromatosis, BRCA1 and 2, tuberous sclerosis, Von-Hippel-Lindau, familial melanoma
Most genes responsible for dominantly inherited cancer syndromes are tumour suppressor genes because the second hit occurs after birth