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A family of sequencing scores that read the scars a broken DNA repair system leaves across a tumour's genome; a high score qualifies ovarian cancer patients for PARP inhibitor maintenance even without a BRCA mutation.
What they measure. When homologous recombination fails, the genome accumulates a characteristic pattern of large deletions, loss of heterozygosity and rearranged chromosome ends. Scar scores count these footprints from tumour sequencing. The Myriad myChoice genomic instability score adds up loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions; FoundationOne CDx reports a genome-wide loss of heterozygosity percentage; HRDetect (Nature Medicine 2017) weighs mutational signatures, including signature 3 and small deletions with microhomology, from whole-genome data; and academic and regional laboratories run their own versions on targeted panels or low-pass genomes. All are reported with a threshold that calls the tumour HRD positive or negative.
Who should have it. Guidelines recommend tumour HRD testing at diagnosis of advanced high-grade ovarian cancer to decide maintenance treatment. In PRIMA (niraparib) and PAOLA-1 (olaparib plus bevacizumab), the benefit of PARP inhibitor maintenance was concentrated in HRD-positive tumours, and the drug labels in Europe are written around that status. Use in breast, prostate and pancreatic cancer is investigational; there the decision still rests on BRCA and related gene mutations.
What changes. HRD positive without a BRCA mutation opens PARP inhibitor maintenance; HRD negative usually means bevacizumab alone or observation, though a share of HRD-negative patients still respond. The scar is permanent: it stays after the tumour restores repair and becomes resistant, so a positive score in relapsed disease overstates current sensitivity, which is where functional assays such as the RAD51 test aim to help. The thresholds differ between assays, so a tumour can be positive on one test and negative on another.
Regulatory status and cost. myChoice CDx is FDA approved as a companion diagnostic; several kit-based European tests are CE marked. The test is a tumour-tissue sequencing assay with a turnaround of two to four weeks, priced in the range of a comprehensive genomic panel, and covered by many health systems for ovarian cancer.
Count genome-wide footprints of failed homologous recombination (loss of heterozygosity, telomeric allelic imbalance, large-scale transitions, mutational signature 3) from tumour sequencing and call HRD against a validated threshold.
One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
This paper set the HRD score threshold the myChoice assay still uses and showed that genomic scars extend platinum sensitivity beyond BRCA carriers in early TNBC, though the TNT trial later found the same score did not predict carboplatin benefit in advanced disease.
Query for this technology: (TITLE:"HRD genomic scar scores" OR ABSTRACT:"HRD genomic scar scores" OR TITLE:"GIS, LOH, HRDetect" OR ABSTRACT:"GIS, LOH, HRDetect" OR TITLE:"genomic instability score" OR ABSTRACT:"genomic instability score" OR TITLE:"LOH score" OR ABSTRACT:"LOH score") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HRD genomic scar scores (GIS, LOH, HRDetect), not a curated reading list.
Shares HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer, myChoice CDx, High-grade serous ovarian cancer.
Shares STRIDE DNA break detection (intoDNA), RAD51 foci assay (functional HRD test), HRD & BRCA testing, Ovarian cancer.
Shares Myriad Genetics, HRD & BRCA testing, Companion diagnostics, PARP.
Shares HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, myChoice CDx, FoundationOne CDx / Liquid CDx, High-grade serous ovarian cancer.
Shares PAOLA-1 / ENGOT-ov25, HRD & BRCA testing, PARP, PARP inhibitors.
Shares HRD & BRCA testing, Homologous recombination deficiency (HRD), PARP, PARP inhibitors.
Shares High-grade serous ovarian cancer, Niraparib, Homologous recombination deficiency (HRD), PARP.
Shares PAOLA-1 / ENGOT-ov25, HRD & BRCA testing, Niraparib, Homologous recombination deficiency (HRD).
Open-source projects that implement or serve this technology, from OnCo's own catalogue: licence and last activity as the repository reported them on the day of the fetch. Listing is not endorsement; check the licence before reuse and the validation before clinical use.
Computes the genomic scar scores (LOH, telomeric allelic imbalance, large-scale transitions) that define an HRD score from copy-number data.
The Nik-Zainal group's R library for mutational signature analysis, including HRDetect, the whole-genome classifier of homologous recombination deficiency.
Commercial and regulated products that serve this technology. Each card says what is behind it: a regulator's database, the literature, a public body's list, or only the company's own words. Listing is not endorsement, and a clearance is a regulatory fact, not a clinical one.
A cloud analysis and interpretation platform hospitals send their sequencing data to, with its own algorithms for variant calling and for scores such as homologous recombination deficiency.