A 38-year-old woman presents with a family history of colorectal cancer (mother diagnosed at age 42, maternal uncle at 45). She undergoes colonoscopy and is found to have a right-sided colon adenocarcinoma. Immunohistochemistry shows loss of MLH1 and MSH2 expression. The condition marked **C** in the diagram is suspected. Which of the following molecular features is the PRIMARY DRIVER of carcinogenesis in this syndrome?
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