Gutenberg Open Science: A novel targeted NGS panel identifies numerous homologous recombination deficiency (HRD)-associated gene mutations in addition to known BRCA mutations

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9948

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DC Field	Value	Language
dc.contributor.author	Vogel, Anna	-
dc.contributor.author	Haupts, Anna	-
dc.contributor.author	Kloth, Michael	-
dc.contributor.author	Roth, Wilfried	-
dc.contributor.author	Hartmann, Nils	-
dc.date.accessioned	2024-01-23T08:55:40Z	-
dc.date.available	2024-01-23T08:55:40Z	-
dc.date.issued	2024	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/9966	-
dc.description.abstract	Deleterious mutations in the BRCA1 and BRCA2 genes have significant therapeutic relevance in clinical settings regarding personalized therapy approaches. BRCA1 and BRCA2 play a pivotal role in homologous recombination (HR) and thus are sensitive for PARP inhibitors (PARPi). Beyond the narrow scope of evaluating only the BRCA mutation status, PARPi can be beneficial for HR deficient (HRD) patients, who harbor mutations in other HR-associated genes. In the present retrospective study, a novel targeted HRD gene panel was validated and implemented for use with FFPE tissue. Samples of patients with ovarian, breast, pancreatic and prostate cancer were included. Variants were robustly detected with various DNA input amounts and the use of test samples showed complete concordance between previously known mutations and HRD panel results. From all the 90 samples included in this cohort, TP53 was the most frequently altered gene (73%). Deleterious BRCA1/2 mutations were found in 20 (22%) of all samples. New pathogenic or likely pathogenic mutations in additional HR-associated genes were identified in 22 (24%) patients. Taken together, the present study proves the feasibility of a new HRD gene panel with reliable panel performance and offers the possibility to easily screen for resistance mutations acquired over treatment time. Mutations in HR-associated genes, besides BRCA1/2, might represent promising potential targets for synthetic lethality approaches. Thus, a substantial number of patients may benefit from expanding the scope of therapeutic agents like PARPi.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	A novel targeted NGS panel identifies numerous homologous recombination deficiency (HRD)-associated gene mutations in addition to known BRCA mutations	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-9948	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Diagnostic pathology	de
jgu.journal.volume	19	de
jgu.pages.alternative	9	de
jgu.publisher.year	2024	-
jgu.publisher.name	BioMed Central	de
jgu.publisher.issn	1746-1596	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1186/s13000-023-01431-8	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	DFG-491381577-H

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