Cited 0 times in
Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 빈진혁 | - |
dc.date.accessioned | 2023-06-23T05:13:45Z | - |
dc.date.available | 2023-06-23T05:13:45Z | - |
dc.date.issued | 2023-05 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/194841 | - |
dc.description.abstract | BRCA1 and BRCA2 both function in DNA double-strand break repair by homologous recombination (HR). Due to their HR defect, BRCA1/2-deficient cancers are sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis), but they eventually acquire resistance. Preclinical studies yielded several PARPi resistance mechanisms that do not involve BRCA1/2 reactivation, but their relevance in the clinic remains elusive. To investigate which BRCA1/2-independent mechanisms drive spontaneous resistance in vivo, we combine molecular profiling with functional analysis of HR of matched PARPi-naive and PARPi-resistant mouse mammary tumors harboring large intragenic deletions that prevent reactivation of BRCA1/2. We observe restoration of HR in 62% of PARPi-resistant BRCA1-deficient tumors but none in the PARPi-resistant BRCA2-deficient tumors. Moreover, we find that 53BP1 loss is the prevalent resistance mechanism in HR-proficient BRCA1-deficient tumors, whereas resistance in BRCA2-deficient tumors is mainly induced by PARG loss. Furthermore, combined multi-omics analysis identifies additional genes and pathways potentially involved in modulating PARPi response. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Cell Press | - |
dc.relation.isPartOf | CELL REPORTS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | BRCA1 Protein / genetics | - |
dc.subject.MESH | BRCA2 Protein / genetics | - |
dc.subject.MESH | BRCA2 Protein / metabolism | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Multiomics | - |
dc.subject.MESH | Neoplasms* / genetics | - |
dc.subject.MESH | Ovarian Neoplasms* / genetics | - |
dc.subject.MESH | Poly(ADP-ribose) Polymerase Inhibitors / pharmacology | - |
dc.subject.MESH | Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use | - |
dc.title | Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) | - |
dc.contributor.googleauthor | Jinhyuk Bhin | - |
dc.contributor.googleauthor | Mariana Paes Dias | - |
dc.contributor.googleauthor | Ewa Gogola | - |
dc.contributor.googleauthor | Frank Rolfs | - |
dc.contributor.googleauthor | Sander R Piersma | - |
dc.contributor.googleauthor | Roebi de Bruijn | - |
dc.contributor.googleauthor | Julian R de Ruiter | - |
dc.contributor.googleauthor | Bram van den Broek | - |
dc.contributor.googleauthor | Alexandra A Duarte | - |
dc.contributor.googleauthor | Wendy Sol | - |
dc.contributor.googleauthor | Ingrid van der Heijden | - |
dc.contributor.googleauthor | Christina Andronikou | - |
dc.contributor.googleauthor | Taina S Kaiponen | - |
dc.contributor.googleauthor | Lara Bakker | - |
dc.contributor.googleauthor | Cor Lieftink | - |
dc.contributor.googleauthor | Ben Morris | - |
dc.contributor.googleauthor | Roderick L Beijersbergen | - |
dc.contributor.googleauthor | Marieke van de Ven | - |
dc.contributor.googleauthor | Connie R Jimenez | - |
dc.contributor.googleauthor | Lodewyk F A Wessels | - |
dc.contributor.googleauthor | Sven Rottenberg | - |
dc.contributor.googleauthor | Jos Jonkers | - |
dc.identifier.doi | 10.1016/j.celrep.2023.112538 | - |
dc.contributor.localId | A06454 | - |
dc.relation.journalcode | J00488 | - |
dc.identifier.eissn | 2211-1247 | - |
dc.identifier.pmid | 37209095 | - |
dc.subject.keyword | BRCA1 | - |
dc.subject.keyword | BRCA2 | - |
dc.subject.keyword | CP: Cancer | - |
dc.subject.keyword | PARP inhibitor | - |
dc.subject.keyword | breast cancer | - |
dc.subject.keyword | homologous recombination | - |
dc.subject.keyword | multi-omics | - |
dc.subject.keyword | therapy resistance | - |
dc.contributor.alternativeName | Bhin, Jinhyuk | - |
dc.contributor.affiliatedAuthor | 빈진혁 | - |
dc.citation.volume | 42 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 112538 | - |
dc.identifier.bibliographicCitation | CELL REPORTS, Vol.42(5) : 112538, 2023-05 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.