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Homologous recombination ceficiency: concepts, definitions, and assays

Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine dip...

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Main Authors: Stewart, Mark D. (Author) , Merino Vega, Diana (Author) , Arend, Rebecca C (Author) , Baden, Jonathan F (Author) , Barbash, Olena (Author) , Beaubier, Nike (Author) , Collins, Grace (Author) , French, Tim (Author) , Ghahramani, Negar (Author) , Hinson, Patsy (Author) , Jelinic, Petar (Author) , Marton, Matthew J (Author) , McGregor, Kimberly (Author) , Parsons, Jerod (Author) , Ramamurthy, Lakshman (Author) , Sausen, Mark (Author) , Sokol, Ethan S (Author) , Stenzinger, Albrecht (Author) , Stires, Hillary (Author) , Timms, Kirsten M (Author) , Turco, Diana (Author) , Wang, Iris (Author) , Williams, J Andrew (Author) , Wong-Ho, Elaine (Author) , Allen, Jeff (Author)
Format: Article (Journal)
Language:English
Published: 27 January 2022
In: The oncologist
Year: 2022, Volume: 27, Issue: 3, Pages: 167-174
ISSN:1549-490X
DOI:10.1093/oncolo/oyab053
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/oncolo/oyab053
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Author Notes:Mark D. Stewart, Diana Merino Vega, Rebecca C. Arend, Jonathan F. Baden, Olena Barbash, Nike Beaubier, Grace Collins, Tim French, Negar Ghahramani, Patsy Hinson, Petar Jelinic, Matthew J. Marton, Kimberly McGregor, Jerod Parsons, Lakshman Ramamurthy, Mark Sausen, Ethan S. Sokol, Albrecht Stenzinger, Hillary Stires, Kirsten M. Timms, Diana Turco, Iris Wang, J. Andrew Williams, Elaine Wong-Ho, Jeff Allen
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Summary:Homologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.Friends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.This publication provides findings from the group’s discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.Overall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.
Item Description:Gesehen am 08.04.2022
Physical Description:Online Resource
ISSN:1549-490X
DOI:10.1093/oncolo/oyab053

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