The HEK293 human cell lineage is widely used in cell biology and biotechnology. We here use whole
genome resequencing of six 293 cell lines to study the dynamics of this aneuploid genome in response
to the manipulations used to generate common 293 cell derivatives, such as transformation and stable
clone generation (293T); suspension growth adaptation (293S) and cytotoxic lectin selection (293SG).
Remarkably, we observe that copy number alteration detection could identify the genomic region that
enabled cell survival under selective conditions (i.c. ricin selection). Furthermore, we present methods
to detect human/vector genome breakpoints and a user-friendly visualization tool for the 293 genome
data. We also establish that the genome structure composition is in steady state for most of these cell
lines when standard cell culturing conditions are used. This resource enables novel and more informed
studies with 293 cells, and we will distribute the sequenced cell lines to this effect.