Homologous Recombination Deficiency Scar: Mutations and Beyond—Implications for Precision Oncology
Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and ta...
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| Veröffentlicht in: | Cancers 2022-08, Vol.14 (17), p.4157 |
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| creator | van der Wiel, Alexander M. A Schuitmaker, Lesley Cong, Ying Theys, Jan Van Hoeck, Arne Vens, Conchita Lambin, Philippe Yaromina, Ala Dubois, Ludwig J |
| description | Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline BRCA1/2 mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss. HRD, regardless of BRCA1/2 status, is associated with specific forms of genomic and mutational signatures termed HRD scar. Detection of this HRD scar might therefore be a more reliable biomarker for HRD. This review discusses and compares different methods of assessing HRD and HRD scar, their advances into the clinic, and their potential implications for precision oncology. |
| doi_str_mv | 10.3390/cancers14174157 |
| format | Article |
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A ; Schuitmaker, Lesley ; Cong, Ying ; Theys, Jan ; Van Hoeck, Arne ; Vens, Conchita ; Lambin, Philippe ; Yaromina, Ala ; Dubois, Ludwig J</creator><creatorcontrib>van der Wiel, Alexander M. A ; Schuitmaker, Lesley ; Cong, Ying ; Theys, Jan ; Van Hoeck, Arne ; Vens, Conchita ; Lambin, Philippe ; Yaromina, Ala ; Dubois, Ludwig J</creatorcontrib><description>Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline BRCA1/2 mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss. HRD, regardless of BRCA1/2 status, is associated with specific forms of genomic and mutational signatures termed HRD scar. Detection of this HRD scar might therefore be a more reliable biomarker for HRD. This review discusses and compares different methods of assessing HRD and HRD scar, their advances into the clinic, and their potential implications for precision oncology.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14174157</identifier><identifier>PMID: 36077694</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Ataxia ; Biomarkers ; BRCA1 protein ; Breast cancer ; Cancer ; Care and treatment ; Cell cycle ; Clinical trials ; DNA damage ; DNA methylation ; DNA repair ; Gene expression ; Health aspects ; Homologous recombination ; Kinases ; Methods ; Mutation ; Mutation (Biology) ; Oncology ; Ovarian cancer ; Patients ; Precision medicine ; Prostate cancer ; Review ; Tumors</subject><ispartof>Cancers, 2022-08, Vol.14 (17), p.4157</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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| subjects | Ataxia Biomarkers BRCA1 protein Breast cancer Cancer Care and treatment Cell cycle Clinical trials DNA damage DNA methylation DNA repair Gene expression Health aspects Homologous recombination Kinases Methods Mutation Mutation (Biology) Oncology Ovarian cancer Patients Precision medicine Prostate cancer Review Tumors |
| title | Homologous Recombination Deficiency Scar: Mutations and Beyond—Implications for Precision Oncology |
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