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The Role of Gene Fusion in Cancer
Gene fusion plays a crucial role in cancer development and treatment, representing a significant type of somatic mutation. Compared to point mutations, gene fusions more accurately reflect the genomic instability of tumors. Studies indicate that gene fusions are widely present across various cancer types, driving approximately 16.5% of cancer cases and serving as the sole driver in over 1% of cases. Around 6% of cases harbor actionable gene fusions.
Impact on Gene Expression
Gene fusion events are typically associated with altered expression of one or two fusion gene partners. Oncogenic genes tend to exhibit overexpression, while tumor suppressor genes may show reduced expression. For instance, fusion proteins involving oncogenes such as EGFR, ERBB2, or RET demonstrate increased expression of these genes. However, the expression patterns of most tumor suppressor genes vary inconsistently across different cancer types, generally trending towards reduced expression.
FDA-Approved Targeted Therapies
In clinical solid tumors, the FDA has approved multiple targeted therapies for treating gene fusions involving ALK, ROS1, RET, MET exon 14 skipping mutations, FGFR2, and NTRK1/2/3. The pathogenic mechanisms of gene fusion include dysregulation of gene transcription control and the production of functionally aberrant chimeric proteins, leading to inactivation of tumor suppressor genes and loss of protein function, thereby promoting cancer initiation and progression.