**Core Concept**
Ewing's sarcoma is a rare type of cancer that primarily affects bones or the soft tissue around the bones. It is characterized by a translocation involving the EWS gene, leading to the formation of a chimeric protein that disrupts normal cellular function.

**Why the Correct Answer is Right**
The most common mutation in Ewing's sarcoma is the t(11;22) translocation, which creates a fusion gene involving the EWS (Ewing Sarcoma) gene on chromosome 22 and the FLI1 (Friend leukemia integration 1) gene on chromosome 11. This results in the production of an aberrant EWS-FLI1 fusion protein that plays a crucial role in the pathogenesis of Ewing's sarcoma. The EWS-FLI1 protein acts as a transcriptional activator, leading to the deregulation of various target genes involved in cell proliferation, survival, and differentiation.

**Why Each Wrong Option is Incorrect**
**Option A:** Other chromosomal translocations, such as t(21;22), can also occur in Ewing's sarcoma, but they are less common than the t(11;22) translocation.
**Option B:** The t(8;21) translocation is characteristic of acute myeloid leukemia (AML), not Ewing's sarcoma.
**Option C:** The t(9;22) translocation is associated with chronic myeloid leukemia (CML), not Ewing's sarcoma.

**Clinical Pearl / High-Yield Fact**
The EWS-FLI1 fusion protein is a critical diagnostic marker for Ewing's sarcoma, and its detection can aid in the differential diagnosis of this cancer from other bone and soft tissue tumors.

**Correct Answer:** C. t(11;22)