biostudies-literaturePishas KICancer Council VictoriaVictorian Cancer AgencyUS National Cancer Institute U54NHMRCNational Health and Medical Research CouncilTherapeutic Innovation Australia Pipeline Accelerator GrantNHMRC CJ Martin Overseas Biomedical FellowshipCancer Systems Biology Center U54 grant5644https://www.ebi.ac.uk/biostudies/studies/S-EPMC8616176biostudies-literatureUnknown13(22)Despite high response rates to initial chemotherapy, the majority of women diagnosed with High-Grade Serous Ovarian Cancer (HGSOC) ultimately develop drug resistance within 1-2 years of treatment. We previously identified the most common mechanism of acquired resistance in HGSOC to date, transcriptional fusions involving the ATP-binding cassette (ABC) transporter <i>ABCB1</i>, which has well established roles in multidrug resistance. However, the underlying biology of fusion-positive cells, as well as how clonal interactions between fusion-negative and positive populations influences proliferative fitness and therapeutic response remains unknown. Using a panel of fusion-negative and positive HGSOC single-cell clones, we demonstrate that in addition to mediating drug resistance, <i>ABCB1</iCancersPhenotypic Consequences of <i>SLC25A40-ABCB1</i> Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer.PMC8616176APP1111032APP1161198ECSG15012APP1184894APP1124309-U54CA209978Simpson KJCheasley DCowley KJVary RShembrey CEGriffiths JIBowtell DDLPishas KICampbell IHoang TLuu JSmith LKChristie ELRashoo NWhite MOBild APandey ABeach JAfalsePhenotypic Consequences of <i>SLC25A40-ABCB1</i> Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer.Despite high response rates to initial chemotherapy, the majority of women diagnosed with High-Grade Serous Ovarian Cancer (HGSOC) ultimately develop drug resistance within 1-2 years of treatment. We previously identified the most common mechanism of acquired resistance in HGSOC to date, transcriptional fusions involving the ATP-binding cassette (ABC) transporter <i>ABCB1</i>, which has well established roles in multidrug resistance. However, the underlying biology of fusion-positive cells, as well as how clonal interactions between fusion-negative and positive populations influences proliferative fitness and therapeutic response remains unknown. Using a panel of fusion-negative and positive HGSOC single-cell clones, we demonstrate that in addition to mediating drug resistance, <i>ABCB1</i2021-01-01T00:00:00Z2021 Nov2026-06-21T03:10:51.657Z2022-02-11T13:16:17.151ZS-EPMC86161763483079710.3390/cancers13225644