Aneuploidy — whole-chromosome or whole-arm DNA imbalances — is the most prevalent and earliest described somatic alteration in cancer. Some but not all common aneuploidies are associated with validated cancer-related genes. Prior studies have extensively characterized patterns of aneuploidy across and within cancer types, and have also shown its fitness advantage in certain cellular contexts. However, whether selective or mechanical biases (e.g., frequent chromosome mis-segregation or rearrangements) are the main drivers of aneuploidy in cancer remains contentious.

To address this question, we developed BISCUT (breakpoint identification of significant cancer undiscovered targets), which detects genomic loci that are subject to fitness advantages or disadvantages by interrogating the length distributions of partial somatic copy-number alterations (partial SCNAs; i.e., centromere- or telomere-bounded amplifications or deletions that do not encompass the entire chromosome arm). Distinct from both aneuploidies and focal SCNAs, partial SCNAs contribute new information not only to uncover loci of selection but also to quantify selective and mechanical pressures behind aneuploidies in cancer.