Characterization of driver mutations in the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene
Sprache des Vortragstitels:
European Society of Human Genetics
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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
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].
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].
The identified variants found at low levels might contribute to tumor development creating a
microenvironment that promotes malignancy.