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HRD Assays: Lines of Research
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Next-generation sequencing assays. Gene expression analysis
.
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BROCA: analysis of mutations of key HR genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2,
FAM175A, MRE11A, NBN, PALB2, RAD51C, RAD51D).
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60-genes signature of “BRCAness”…
High correlation with response to platinum-based therapy an overall survival. NOT VALIDATED.
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Functional ex-vivo assays:
RAD51 nuclear foci
formation by immunofluorescence or other DNA repair
complexes by immunohistochemistry
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PRO: Dynamic and functional biomarker
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CON: Requires fresh tissue. Reproducibility.
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Genome scars.
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ARIEL 2. Rucaparib and
genomic LOH
assay (Foundation Medicine)
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NOVA trial. Niraparib and
HRD score
(myChoice HRDTM Myriad)
Pennington Clin Cancer Res 2013. Mukhopadhyay Clin Cancer Res 2010. Graeser Clin Cancer Res 2010. Kristeleit ECCO 2015. Mirza ESMO 2016