Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences of the United States of America. 1971;68:820-3. PMID 5279523

One-paragraph summary

Knudson compared age-incidence patterns in 48 cases and published series, proposing that malignant transformation requires two mutational events.

Key findings

• In inherited disease the first event is constitutional and the second somatic; in non-hereditary disease both are somatic.
• The model explained bilateral, multifocal, unilateral and nonpenetrant carrier phenotypes with a mean of about three tumours per carrier.

Limitations

• It was an inferential statistical model before RB1 was cloned; it does not identify the cell of origin or every progression event.

Why it matters

The paper created the conceptual tumor-suppressor framework and remains the load-bearing model for counselling and laterality.

Cited by wiki pages

• overview
• rb1 genetics and heritability
• molecular pathogenesis and cell of origin