{"doi":"10.1101/2020.06.18.159095","title":"Whole genome doubling confers unique genetic vulnerabilities on tumor cells","abstract":"Summary Whole genome doubling (WGD) occurs early in tumorigenesis and generates genetically unstable tetraploid cells that fuel tumor development. Cells that undergo WGD (WGD + ) must adapt to accommodate their abnormal tetraploid state; however, the nature of these adaptations, and whether they confer vulnerabilities that can subsequently be exploited therapeutically, is unclear. Using sequencing data from ∼10,000 primary human cancer samples and essentiality data from ∼600 cancer cell lines, we show that WGD gives rise to common genetic traits that are accompanied by unique vulnerabilities. We reveal that WGD + cells are more dependent on spindle assembly checkpoint signaling, DNA replication factors, and proteasome function than WGD − cells. We also identify KIF18A , which encodes for a mitotic kinesin, as being specifically required for the viability of WGD + cells. While loss of KIF18A is largely dispensable for accurate chromosome segregation during mitosis in WGD − cells, its loss induces dramatic mitotic errors in WGD + cells, ultimately impairing cell viability. Collectively, our results reveal new strategies to specifically target WGD + cancer cells while sparing the normal, non-transformed WGD − cells that comprise human tissue.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120930,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559978,"name":"Amanda DiDomizio","orcid":null,"position":1,"is_corresponding":false},{"id":559979,"name":"Marc A. Vittoria","orcid":null,"position":2,"is_corresponding":false},{"id":559980,"name":"Carlos J. Ticas","orcid":null,"position":3,"is_corresponding":false},{"id":109417,"name":"Sheena Patel","orcid":null,"position":4,"is_corresponding":false},{"id":282472,"name":"Yusuke Koga","orcid":"0000-0003-4875-6598","position":5,"is_corresponding":false},{"id":559314,"name":"Kristýna Kotýnková","orcid":"0000-0003-2066-9505","position":6,"is_corresponding":false},{"id":559315,"name":"Jasmine Vakhshoorzadeh","orcid":"0000-0001-5417-8865","position":7,"is_corresponding":false},{"id":559981,"name":"Nicole Hermance","orcid":null,"position":8,"is_corresponding":false},{"id":559316,"name":"Taruho S. Kuroda","orcid":"0000-0001-6693-4496","position":9,"is_corresponding":false},{"id":559982,"name":"Neha Parulekar","orcid":null,"position":10,"is_corresponding":false},{"id":69693,"name":"Alison M. Taylor","orcid":"0000-0001-9341-535X","position":11,"is_corresponding":false},{"id":559317,"name":"Amity L. Manning","orcid":"0000-0003-1332-9086","position":12,"is_corresponding":false},{"id":225132,"name":"Joshua D. Campbell","orcid":"0000-0003-0780-8662","position":13,"is_corresponding":false},{"id":559318,"name":"Neil J. Ganem","orcid":"0000-0003-0269-6585","position":14,"is_corresponding":false},{"id":559977,"name":"Ryan J. Quinton","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}