TY  - JOUR
AU  - Menzel, Michael
AU  - Endris, Volker
AU  - Schwab, Constantin
AU  - Kluck, Klaus
AU  - Neumann, Olaf
AU  - Beck, Susanne
AU  - Ball, Markus
AU  - Schaaf, Christian
AU  - Fröhling, Stefan
AU  - Lichtner, Peter
AU  - Schirmacher, Peter
AU  - Kazdal, Daniel
AU  - Stenzinger, Albrecht
AU  - Budczies, Jan
TI  - Accurate tumor purity determination is critical for the analysis of homologous recombination deficiency (HRD).
JO  - Translational oncology
VL  - 35
SN  - 1944-7124
CY  - Ann Arbor, Mich.
PB  - [Verlag nicht ermittelbar]
M1  - DKFZ-2023-01195
SP  - 101706
PY  - 2023
AB  - 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
KW  - HRD (Other)
KW  - Homologous recombination deficiency (Other)
KW  - Tumor cell content (Other)
KW  - Tumor purity (Other)
KW  - WES (Other)
KW  - Whole exome sequencing (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37327584
DO  - DOI:10.1016/j.tranon.2023.101706
UR  - https://inrepo02.dkfz.de/record/276893
ER  -