What effect does a "first hit" on a tumor-suppressor gene have?

The concept of a "first hit" on a tumor-suppressor gene refers to the initial genetic alteration that affects the function of that gene. Tumor-suppressor genes play a critical role in regulating cell growth and preventing tumor formation, typically by producing proteins that help to control cell division and maintain genomic integrity.

When a first hit occurs, such as a mutation or deletion in a tumor-suppressor gene, the function of that gene can be compromised, but it often does not immediately lead to cancer. For tumor-suppressor genes, both alleles (copies of the gene) must be inactivated to promote uncontrolled cell growth. This is known as the "two-hit hypothesis," which was first proposed by Alfred Knudson in relation to retinoblastoma.

Thus, while the first hit weakens the gene's normal protective functions, a second hit, which inactivates the remaining functional allele, is typically required to result in the loss of control over cell proliferation. This progression is essential in the development of many cancers, as the accumulation of additional genetic changes often contributes to tumorigenesis. Therefore, the idea that a "first hit" necessitates a subsequent alteration (the second hit) to cause abnormal growth is fundamental to the