# HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures

Source: https://onco.cc/key-papers/paper-davies-nat-med/  
OnCo record `paper-davies-nat-med` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one technology page, indexed on Europe PMC as PubMed record 28288110 and published in Nature Medicine; the citing page links this DOI, which is how the record was matched.

## Summary

Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.

Indexed on Europe PMC as PubMed record 28288110 (DOI 10.1038/nm.4292). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature Medicine
- Year: 2017
- DOI: 10.1038/nm.4292
- Authors: Davies H, Glodzik D, Morganella S, et al.
- What it means: 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.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Nat Med 2017: https://doi.org/10.1038/nm.4292
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28288110/
- Europe PMC: https://europepmc.org/article/MED/28288110

## Connected records

- technologies: [HRD genomic scar scores (GIS, LOH, HRDetect)](https://onco.cc/technologies/hrd-genomic-scar-scores/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

---
JSON: https://onco.cc/api/v1/entities/paper-davies-nat-med.json