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Mechanistic and therapeutic implications of spliceosomal gene mutations in ER+ breast cancer

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Technical Report,15 Aug 2018,14 Aug 2019

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Sloan Kettering Institute for Cancer Research New York United States

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Recent evidence has revealed that altered mRNA splicing is a mechanism by which tumors can derive constitutive, tumor-promoting signals. Recurrent, somatic mutations in the core RNA splicing factor SF3B1 have been found in several malignancies. Through analyses of metastatic breast cancer patients at our center, we have noted hotspot mutations in SF3B1 in up to 6 of cases and these are associated with the ERHER2- subtype and inferior outcomes in patients. We therefore conducted studies to understand the potential implications of SF3B1 mutations on breast cancer pathogenesis and found that expression of the most common mutant, K700E, led to alterations in RNA splicing and promoted hormone-independent proliferation of ER cells. Based on these initial observations, we are now studying the consequences of SF3B1 mutation on breast tumorigenesis, cancer progression, and sensitivity to spliceosomal targeted therapy.

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  • Medicine and Medical Research

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