Mutation and cancer: statistical study of retinoblastoma
Open accessAbstract
Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.
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The genetic and epigenetic defects transmitted at birth explain the predisposition according to the first hit-second hit hypothesis in oncology.
“The genetic and epigenetic defects transmitted at birth explain the predisposition according to the first hit-second hit hypothesis (255) in oncology.”
From Pathogenesis of endometriosis: The genetic/epigenetic theory (2019) · cites this paper as [255]
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- Authors
- Knudson, A. G.
- Affiliations
- The University of Texas System (US)
- Corresponding author
- Knudson, Alfred G.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1971-04
- Volume
- 68
- Issue
- 4
- Pages
- 820-823
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC389051
- OpenAlex
- W2077858999
- Cited by
- 7,612
- References
- 11
- Citations by year
- 2026: 128 · 2025: 191 · 2024: 188 · 2023: 239 · 2022: 212 · 2021: 257 · 2020: 251 · 2019: 196 · 2018: 200 · 2017: 213 · 2016: 212 · 2015: 221 · 2014: 234 · 2013: 217 · 2012: 244
- FWCI
- 64.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- retinoblastoma, two-hit hypothesis, somatic mutations, germline mutations, mutation rate estimation, Poisson distribution, bilateral retinoblastoma, multiple tumors, hereditary cancer, tumor multiplicity
- MeSH terms
- Child, Preschool, Eye Neoplasms, Female, Humans, Infant, Functional Laterality, Male, Mutation, Retinoblastoma, Retrospective Studies, Statistics as Topic
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