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Background

Loss of heterozygosity (LOH) is a frequent event in cancer, that is caused by larger chromosomal deletions in cancer cells due to genetic instability [TS1](Mertens et al., 1997). Thus heterozygous individuals become hemi-or homozygous for certain genes, which might change the phenotype of a cancer cell compared to normal cells (Muller et al., 2012),(Dey et al., 2017). This change might create an opportunity to selectively target cancer cells while sparing normal cells (Rendo et al., 2020).

Methods

To find potential drug targets, data from the 1000 Genomes project was analyzed to identify prevalent constitutional loss-of-function (LoF) SNPs in coding regions causing truncating or splice site mutations with allele frequency> 0.5 [TS1][NR2]%, heterozygosity between 10% and 90% of potential relevance in cancer cells. The drug metabolic gene CYP2D6 was selected and isogenic cell models were …