Journal article
The two-stage mutation model in retinal hemangioblastoma
Ophthalmic genetics, Vol.19(3), pp.123-130
09/1998
DOI: 10.1076/opge.19.3.123.2185
PMID: 9810567
Abstract
The two-stage mutation model involving successive inactivation of both alleles of a tumor suppressor gene was originally proposed by Knudson, who analyzed the age incidence curves for unilateral and bilateral retinoblastoma, and suggested that hereditary tumors arise by a single somatic event superimposed on a defective genetic background and sporadic tumors by a two-stage somatic process. In this study, the age-incidence curve of patients with retinal hemangioblastoma with and without associated von Hippel-Lindau disease were analyzed. We reviewed the literature between 1964 and 1998 to find all reported cases of retinal hemangioblastoma and classified patients in a type A group (n = 223) when associated with von Hippel-Lindau disease and a type B group (n = 30) when not associated with von Hippel-Lindau disease. We analyzed and compared the age incidence of these two groups. There was a statistically significant difference between the mean age at diagnosis of retinal hemangioblastoma in the two groups, i.e., 48.4 +/- 16.6 years for type B patients and 24.9 +/- 12.0 years for type A patients (p < 0.0001). The age incidence curve for type A retinal hemangioblastoma fit a first-order equation (log S = 0.411-0.034t) with r = 0.97, indicating a single somatic mutation, whereas the age incidence curve for type B retinal hemangioblastoma fit a second-order equation (log S = 0.184-2.25 x 10(-4)t2) with r = 0.97, indicating two somatic mutations. Type B (sporadic) retinal hemangioblastoma may arise from two separate somatic mutations inactivating both alleles at the von Hippel-Lindau locus, whereas patients with von Hippel-Lindau disease (type A) inherit a defective allele and require only one additional somatic mutation.
Details
- Title: Subtitle
- The two-stage mutation model in retinal hemangioblastoma
- Creators
- Joseph H Chang - Emory UniversityChristoph W SpraulMichael L LynnArlene DrackHans E Grossniklaus
- Resource Type
- Journal article
- Publication Details
- Ophthalmic genetics, Vol.19(3), pp.123-130
- Publisher
- England
- DOI
- 10.1076/opge.19.3.123.2185
- PMID
- 9810567
- ISSN
- 1381-6810
- eISSN
- 1744-5094
- Grant note
- EY06030 / NEI NIH HHS
- Language
- English
- Date published
- 09/1998
- Academic Unit
- Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences
- Record Identifier
- 9983979906802771
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