Characterization of driver mutations in the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene

Description

Background/Objectives: We adapted duplex sequencing to screen a unique type of mutagenesis that confers a selective growth advantage in ERBB2 gene [1-3]. We hypothesize that a series of driver mutations in this oncogene are expanding in sperm and testis. Some of these mutations lead to aberrant ERBB signaling that could induce the clonal expansion of mutant germ cells with paternal age and testis specific-mosaicism. Methods: Further, we characterized the clonal expansion of candidate hotspot mutations in the testis by droplet digital PCR (ddPCR), along with the analysis of the functional changes in the downstream activation of the ERBB2 signaling pathway by biophysical methods [4-7]. Results: Some of the mutations were identified as hotspot pathogenic variants that could be expanding at low, sub-clonal levels in the male germline. Further, the functional analysis showed that the selected variants have a significant activation increase compared to the wild-type constructs [6-8]. Conclusion: The identified variants found at low levels might contribute to tumor development creating a microenvironment that promotes malignancy.

Period	11 Jun 2022
Event title	European Society of Human Genetics
Event type	Conference
Location	AustriaShow on map