Alternative NF1 Isoforms in RAS Deregulation and Breast Cancer Progression
Abstract
NF1 function is classically altered by gene deletion in breast cancer. An alternative-but-equallyimportant mechanism of NF1 deficiency is defective mRNA processing whereby mutant mRNA transcriptsdirectly or indirectly affect the stability of wild type transcripts. This delicate balance of mutantversus wild type transcript abundance can dramatically affect protein synthesis and, ultimately, RASsignaling fates. In cancer, dysregulation of alternative splicing promotes malignant progression andtherapeutic resistance by altering the expression and function of tumor suppressors and oncogenes.Little is known about NF1-related mRNA processing or how alternative transcripts affect NF-relatedphenotypes such as breast cancer. Our goal is to define the genetic and isoform changes in NF1 thatoccur in breast cancer with the ultimate goal of identifying prognostic biomarkers and targetedtherapeutic strategies for both female and male NF patients with breast cancer. Our hypothesis isthat alternative RNA splicing of NF1 abrogates NF1 gene function and RAS regulation to promote breastcancer progression and therapeutic resistance. Our experimental approaches leverage innovativesequencing methods, our established rat model of Nf1-deficient breast cancer, and comprehensiveanalysis of breast cancer datasets.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1178589
Entities
People
- Matthew R. Steensma