Mechanistic and Therapeutic Implications of Spliceosomal Gene Mutations in ER+ Breast Cancer
Abstract
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 inseveral malignancies. Through analyses of metastatic breast cancer patients at our center, we have noted hotspotmutations in SF3B1 in up to 6% of cases and these are strongly associated with the ER+/HER2- subtype and inferioroutcomes in patients. We therefore conducted studies to understand the potential implications of SF3B1 mutations onbreast cancer pathogenesis and have so far found that expression of the most common mutant, K700E, leads tocharacteristic alterations in RNA splicing, promotes the invasiveness and lethality of PIK3CA mutant breast cancer, andincreases the sensitivity of PIK3CA mutant breast cancer cells to AKT inhibition. Based on these observations, we arefurther studying the consequences of SF3B1 mutation on breast cancer progression and sensitivity to spliceosomaltargeted therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1114508
Entities
People
- Omar Abdel-Wahab
Organizations
- Memorial Sloan Kettering Cancer Center