‘Knudson’s two-hit’ hypothesis is associated with-
**Core Concept**
Knudson's two-hit hypothesis is a fundamental concept in cancer genetics, proposing that the development of cancer requires two mutational events (hits) in a tumor suppressor gene. This hypothesis was first proposed by Alfred Knudson in 1971 and has since become a cornerstone in understanding the pathogenesis of retinoblastoma and other cancers.
**Why the Correct Answer is Right**
The two-hit hypothesis is based on the idea that a normal cell has two copies of a tumor suppressor gene, one inherited from each parent. The first hit, or mutation, in one of the two copies of the gene leads to a loss of function, but the second copy remains intact. The second hit, or subsequent mutation, inactivates the remaining functional copy, leading to the loss of tumor suppressor function and the development of cancer. This hypothesis has been extensively validated in the context of retinoblastoma, where mutations in the RB1 gene are a hallmark of the disease.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it does not specify the key aspect of the two-hit hypothesis, which is the requirement of two mutational events in a tumor suppressor gene.
**Option B:** This option is incorrect because it is a different hypothesis related to cancer development, and does not accurately describe the two-hit hypothesis proposed by Knudson.
**Option C:** This option is incorrect because it is a general statement about cancer genetics, but does not specifically relate to Knudson's two-hit hypothesis.
**Clinical Pearl / High-Yield Fact**
Knudson's two-hit hypothesis highlights the importance of tumor suppressor genes in preventing cancer and emphasizes the need for two mutational events to lead to cancer development. This concept has far-reaching implications for our understanding of cancer genetics and has been instrumental in the development of targeted cancer therapies.
**Correct Answer: A. Retinoblastoma**