Exploring the Pathogenic and Therapeutic Implications of Aberrant Splicing in Breast Cancer
Abstract
In this proposal, we set out to a) systematically monitor splicing variant profiles in breast cancer susceptibility genes and b) explore the role of alternative splicing in breast chemotherapy using a global strategy. In doing so, we hope to identify and validate candidate splicing variants involved in tumorigenesis using polony digital exon-profiling and functional assays. We are moving forward on four fronts - 1) the barcode methodology is in development; 2) we are working with state-of-the art capture arrays; 3) we are using the very latest RNA sequencing technology and 4) we are conducting comprehensive analyses of existing splice site variants in known breast cancer susceptibility genes. In part 3, we have generated over 5 million reads that have been aligned to the splice junction libraries, and we are using these reads to quantify and characterize alternative splicing events. Moreover, we will add value to this project by attempting to identify fusion proteins. In part 4, we have determined that the BRCA2 isoform known as BRCA2deltaex12 is not associated with a recognizable phenotype. This work is now in press in Human Mutation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2009
- Accession Number
- ADA535367
Entities
People
- Jacek Majewski
- William David Foulkes
Organizations
- Jewish General Hospital