What genetic mutation is most frequently associated with osteosarcoma?

The P53 gene mutation is significantly associated with osteosarcoma due to its critical role in regulating the cell cycle and maintaining genomic stability. The P53 protein functions as a tumor suppressor, and mutations in this gene can lead to uncontrolled cell growth, which is a hallmark of cancer. In many types of cancers, including osteosarcoma, mutations in the P53 gene disrupt its normal function, allowing for the accumulation of additional genetic abnormalities that can drive tumor progression.

In osteosarcoma specifically, P53 mutations are often found in both human cases and in spontaneous models of the disease, making it a central focus in understanding the pathology and potential treatment avenues for this type of bone cancer.

In contrast, other mutations or gene amplifications listed, such as BRCA1, KRAS, or MYC, are less directly linked with osteosarcoma pathogenesis compared to P53. Each of those genes may be involved in different cancers or may play different roles in signaling pathways, but the association of P53 mutations with osteosarcoma is particularly well-documented in the literature. This makes it the most relevant choice when considering genetic alterations frequently observed in this malignancy.