recognized for his groundbreaking “two-hit” hypothesis, ..

N2 - Two nuclear families showing characteristics of the SBLA syndrome are described wherein progeny of breast cancer-affected mothers manifested early childhood malignant neoplasms. These observations have led us to postulate a novel type genetic-environmental interactive model which incorporates Knudsen's "two-hit" hypothesis as a partial explanation for the exceedingly early onset of cancer in the subject progeny. Given the assumption that the first hit was germinal with transfer of the deleterious SBLA gene at conception, we postulate that the second or somatic-hit occurred early on in utero. This may have involved a complex mechanism of one or more factors including tumor cell products, tumor specific antigens, immunosuppression, de-repressed oncogene, or an activated oncogenic virus via a transplacental communicable phenomenon. The testing of this new hypothesis dealing with carcinogenesis in the SBLA syndrome should employ immunological-genetic parameters concurrently in fetuses and mothers.

The Knudson hypothesis, also known as the two-hit hypothesis or multiple-hit hypothesis, ..

AB - Two nuclear families showing characteristics of the SBLA syndrome are described wherein progeny of breast cancer-affected mothers manifested early childhood malignant neoplasms. These observations have led us to postulate a novel type genetic-environmental interactive model which incorporates Knudsen's "two-hit" hypothesis as a partial explanation for the exceedingly early onset of cancer in the subject progeny. Given the assumption that the first hit was germinal with transfer of the deleterious SBLA gene at conception, we postulate that the second or somatic-hit occurred early on in utero. This may have involved a complex mechanism of one or more factors including tumor cell products, tumor specific antigens, immunosuppression, de-repressed oncogene, or an activated oncogenic virus via a transplacental communicable phenomenon. The testing of this new hypothesis dealing with carcinogenesis in the SBLA syndrome should employ immunological-genetic parameters concurrently in fetuses and mothers.


UK ONCOGENOMICS The seminal ‘two-hit hypothesis ’ implicitly ..

Knudsen’s “two-hit” hypothesis, ..