The anaphase-promoting complex: A key mitotic regulator associated with somatic mutations occurring in cancer.

Abstract

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that helps control chromosome separation and exit from mitosis in many different kinds of organisms, including yeast, flies, worms, and humans. This review represents a new perspective on the connection between APC/C subunit mutations and cancer. The complex nature of APC/C and limited mutation analysis of its subunits has made it difficult to determine the relationship of each subunit to cancer. In this work, cancer genomic data were examined to identify APC/C subunits with a greater than 5% alteration frequency in 11 representative cancers using the cBioPortal database. Using the Genetic Determinants of Cancer Patient Survival database, APC/C subunits were also studied and found to be significantly associated with poor patient prognosis in several cases. In comparing these two kinds of cancer genomics data to published large-scale genomic analyses looking for cancer driver genes, ANAPC1 and ANAPC3/CDC27 stood out as being represented in all three types of analyses. Seven other subunits were found to be associated both with >5% alteration frequency in certain cancers and being associated with an effect on cancer patient prognosis. The aim of this review is to provide new approaches for investigators conducting in vivo studies of APC/C subunits and cancer progression. In turn, a better understanding of these APC/C subunits and their role in different cancers will help scientists design drugs that are more precisely targeted to certain cancers, using APC/C mutation status as a biomarker.