Legacy Genetic Testing Results for Cancer Susceptibility: How Common are Conflicting Classifications in a Large Variant Dataset from Multiple Practices?

Purpose: The classification of germline variants may differ between labs and change over time. We apply a variant harmonization tool, Ask2Me VarHarmonizer, to map variants to ClinVar and identify discordant variant classifications in a large multipractice variant dataset.

Methods: A total of 7496 variants sequenced between 1996 and 2019 were collected from 11 clinical practices.

MET and ERBB2 are coexpressed in ERBB2+ breast cancer and contribute to innate resistance.

Unlabelled: Breast cancer displays significant intratumoral heterogeneity, which has been shown to have a substantial impact on both innate and acquired resistance to tyrosine kinase inhibitors. The heterogeneous expression of multiple receptor tyrosine kinases (RTK) in cancers supports tumor signaling robustness and plays a significant role in resistance to targeted inhibition. Recent studies have revealed interactions between the MET receptor and the ERBB receptor family in the therapeutic resistance of several cancers.