Figure 2.

The origins, types, and consequences of ASE in cancer. ASE can have both a germline or somatic origin (Left panel). The former refers to the case where genetic alterations are inherited from the parents, and the latter when these are acquired during the lifetime of the individual. Germline and somatic alterations can be non-coding, when they affect cis-regulatory elements or consist of an aberration in epigenetic mark configuration, or coding when stop-gained or splicing mutations lead to nonsense-mediated decay and preferential wild-type allele expression (middle panel). Copy number alterations, including gene gains and losses, can span both coding and non-coding genetic regions. These alterations can result in tumor-promoting mechanisms, such as higher expression of oncogenes or lower expression of functional tumor suppressors, which can then lead to aberrant cell cycle control, impaired DNA repair response, or other tumor-promoting mechanisms. However, they theoretically may also lead to compensatory mechanisms if the wild-type copy is expressed at higher levels than the mutant copies.