TITLE
Functional analysis of non-amplified/overexpressed HER2 L869R heterozygous in human somatic breast cells
JHU Ref. #
C13782
ABSTRACT
Human epidermal growth factor receptor 2 (HER2) missense mutations have been reported in human cancers and primarily occur in the absence of HER2 gene amplification. Whether these HER2 missense mutations will predict for sensitivity to current HER2-directed therapies is unknown. Johns Hopkins researchers developed gene targeted heterozygous knock in of HER2 L869R mutation found in HER2 non-amplified/overexpressed breast cancer to study the biology of HER2 mutations as single copies for understanding HER2 mutations and strategies to target them.
FEATURES
Johns Hopkins researchers used two HER2 nonamplified human breast epithelial cell lines to create an isogenic panel of HER2 missense knockin mutants. They used the adeno-associated virus (AAV)- mediated gene targeting to create the HER2 L869R mutant knockin in MCF-10A and MCF7 human breast epithelial cells. The advantages are:
This work represents the first isogenic knock in of the HER2 L869R missense mutation allowing for study of this mutation in the non-amplified/overexpressed setting.
This is novel and important since the majority of cancers with HER2 missense mutations do not have amplification/overexpression of the mutant HER2 alleles.
STAGE OF DEVELOPMENT
Tangible material, cell lines that have been genetically modified and are useful for studying the biology and functional relevance of HER2 mutations. The HER2 L869R mutation has been knocked in to MCF-10A and MCF7 cells using rAAV gene targeting
DISEASE INDICATION
Cancers
ASSOCIATED PUBLICATIONS
- Proc Natl Acad Sci U S A. 2015 Nov 10; 112(45): E6205–E6214 -
