Genomic landscape and therapeutic implications of Anaplastic Lymphoma Kinase fusion-positive colorectal cancer
ALK fusions define a rare but biologically distinct subset of colorectal cancer characterized by frequent MSI-high/MMR-deficient status and a unique genomic landscape, supporting the use of ALK-directed therapies.
Background: ALK fusions are established oncogenic drivers in several cancers but are rare in colorectal cancer (CRC). Methods: Comprehensive genomic profiling of 562 advanced CRC tumors identified 63 ALK fusion-positive cases (0.1%). Results: ALK fusion-positive CRC demonstrated enrichment for MSI-high/MMR-deficient status, high tumor mutational burden, and higher PD-L1 expression, while canonical driver mutations (KRAS, APC, PIK3CA) were markedly depleted. Conclusion: ALK fusions define a biologically distinct subset of CRC with frequent MSI-high disease, suggesting a rationale for ALK-directed therapy and emphasizing the importance of genomic profiling in CRC.
Identification of ALK fusions in CRC delineates a unique genomic subtype that may respond to targeted ALK inhibitors and reveals a high prevalence of MSI-high, informing treatment decisions and surveillance strategies.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
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