Genomic dissection and mutation-specific target discovery for breast cancer PIK3CA hotspot mutations.

ABSTRACT:

Background

Recent advancements in high-throughput genomics and targeted therapies have provided tremendous potential to identify and therapeutically target distinct mutations associated with cancers. However, to date the majority of targeted therapies are used to treat all functional mutations within the same gene, regardless of affected codon or phenotype.

Results

In this study, we developed a functional genomic analysis workflow with a unique isogenic cell line panel bearing two distinct hotspot PIK3CA mutations, E545K and H1047R, to accurately identify targetable differences between mutations within the same gene. We performed RNA-seq and ATAC-seq and identified distinct transcriptomic and epigenomic differences associated with each PIK3CA hotspot mutation.

SUBMITTER: Miranda AX 

PROVIDER: S-EPMC10802285 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature