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Status: Bibliographieeintrag

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Verfasst von:Menzel, Michael [VerfasserIn]   i
 Endris, Volker [VerfasserIn]   i
 Schwab, Constantin [VerfasserIn]   i
 Kluck, Klaus [VerfasserIn]   i
 Neumann, Olaf [VerfasserIn]   i
 Beck, Susanne [VerfasserIn]   i
 Ball, Markus [VerfasserIn]   i
 Schaaf, Christian P. [VerfasserIn]   i
 Fröhling, Stefan [VerfasserIn]   i
 Lichtner, Peter [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Kazdal, Daniel [VerfasserIn]   i
 Stenzinger, Albrecht [VerfasserIn]   i
 Budczies, Jan [VerfasserIn]   i
Titel:Accurate tumor purity determination is critical for the analysis of homologous recombination deficiency (HRD)
Verf.angabe:Michael Menzel, Volker Endris, Constantin Schwab, Klaus Kluck, Olaf Neumann, Susanne Beck, Markus Ball, Christian Schaaf, Stefan Fröhling, Peter Lichtner, Peter Schirmacher, Daniel Kazdal, Albrecht Stenzinger, Jan Budczies
E-Jahr:2023
Jahr:September 2023
Umfang:10 S.
Illustrationen:Illustrationen
Fussnoten:Online verfügbar: 14. Juni 2023 ; Gesehen am 03.08.2023
Titel Quelle:Enthalten in: Translational oncology
Ort Quelle:Ann Arbor, Mich. : [Verlag nicht ermittelbar], 2008
Jahr Quelle:2023
Band/Heft Quelle:35(2023) vom: Sept., Artikel-ID 101706, Seite 1-10
ISSN Quelle:1936-5233
Abstract:Homologous recombination deficiency (HRD) is a predictive marker for response to poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian carcinoma. HRD scores have entered routine diagnostics, but the influence of algorithms, parameters and confounders has not been analyzed comprehensively. A series of 100 poorly differentiated ovarian carcinoma samples was analyzed using whole exome sequencing (WES) and genotyping. Tumor purity was determined using conventional pathology, digital pathology, and two bioinformatic methods. HRD scores were calculated from copy number profiles determined by Sequenza and by Sclust either with or without fixed tumor purity. Tumor purity determination by digital pathology combined with a tumory purity informed variant of Sequenza served as reference method for HRD scoring. Seven tumors had deleterious mutations in BRCA1/2, 12 tumors had deleterious mutations in other homologous recombination repair (HRR) genes, 18 tumors had variants of unknown significance (VUS) in BRCA1/2 or other HRR genes, while the remaining 63 tumors had no relevant alterations. Using the reference method for HRD scoring, 68 tumors were HRD-positive. HRDsum determined by WES correlated strongly with HRDsum determined by single nucleotide polymorphism (SNP) arrays (R = 0.85). Conventional pathology systematically overestimated tumor purity by 8% compared to digital pathology. All investigated methods agreed on classifying the deleterious BRCA1/2-mutated tumors as HRD-positive, but discrepancies were observed for some of the remaining tumors. Discordant HRD classification of 11% of the tumors was observed comparing the tumor purity uninformed default of Sequenza and the reference method. In conclusion, tumor purity is a critical factor for the determination of HRD scores. Assistance by digital pathology helps to improve accuracy and imprecision of its estimation.
DOI:doi:10.1016/j.tranon.2023.101706
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1016/j.tranon.2023.101706
 kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S193652332300092X
 DOI: https://doi.org/10.1016/j.tranon.2023.101706
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Homologous recombination deficiency
 HRD
 Tumor cell content
 Tumor purity
 WES
 Whole exome sequencing
K10plus-PPN:1854258958
Verknüpfungen:→ Zeitschrift

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