Mechanisms of tandem duplication in the cancer genome

Ralph Scully; Dominik Glodzik; Francesca Menghi; Edison T Liu; Cheng-Zhong Zhang

doi:10.1016/j.dnarep.2024.103802

Mechanisms of tandem duplication in the cancer genome

DNA Repair (Amst). 2024 Dec 25:145:103802. doi: 10.1016/j.dnarep.2024.103802. Online ahead of print.

Authors

Ralph Scully¹, Dominik Glodzik², Francesca Menghi³, Edison T Liu³, Cheng-Zhong Zhang⁴

Affiliations

¹ Department of Medicine, Division of Hematology-Oncology and Cancer Research Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: rscully@bidmc.harvard.edu.
² Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
³ The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
⁴ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.

PMID: 39742573
DOI: 10.1016/j.dnarep.2024.103802

Abstract

Tandem duplications (TD) are among the most frequent type of structural variant (SV) in the cancer genome. They are characterized by a single breakpoint junction that defines the boundaries and the size of the duplicated segment. Cancer-associated TDs often increase oncogene copy number or disrupt tumor suppressor gene function, and thus have important roles in tumor evolution. TDs in cancer genomes fall into three classes, defined by the size of duplications, and are associated with distinct genetic drivers. In this review, we survey key features of cancer-related TDs and consider possible underlying mechanisms in relation to stressed DNA replication and the 3D organization of the S phase genome.

Keywords: BRCA1; Break-induced replication; Breakage-fusion; CDK12; Cyclin E; Single strand annealing; Sister replication fork; Sister replisome; Structural variant; Tandem duplication.