Homologous recombination deficiency (HRD) testing & tumour BRCA (tBRCA) genomic sequencing in ovarian carcinoma and related FIGO stage III and IV cancers

Homologous recombination deficiency (HRD), resulting from defects in the homologous recombination repair pathway and leading to genomic instability, is a common feature of stage III or IV, high-grade serous or endometrioid ovarian cancer (HGSO), primary peritoneal cancer, or fallopian-tube cancer, and is predictive of sensitivity to poly ADP-ribose polymerase (PARP) inhibitors. HRD status is assessed by HRD genomic instability testing in tumour samples in addition to BRCA1 and BRCA2 mutation (tBRCA) testing by DNA sequencing.

The HRD testing & tBRCA DNA sequencing service was previously funded by a global co-promotion agreement between AstraZeneca & MSD and delivered, in accordance with arrangements agreed with NHSE through NHS Genomic Laboratory Hubs, by Myriad Genetics Inc. in the United States. This arrangement ceases on 31st March 2024, and from 1st April 2024 the service will transition from Myriad Genetics to the North East and Yorkshire Genomic Laboratory Hub (NEY GLH). 

All first line patients with newly diagnosed HGSO and related cancers are eligible for tBRCA sequencing and HRD testing. Relapsed 2nd and 3rd line patients who have not previously had any tBRCA or HRD testing are eligible for tumour BRCA (tBRCA) testing only. The eligibility criteria for tBRCA/HRD testing are described in the National Genomic Test Directory for Cancer:

The eligibility criteria for tBRCA/HRD testing are described in the National Genomic Test Directory for Cancer:

National Genomic Test Directory for Cancer

Table 1.National Genomic Test Directory for cancer: Inclusions for HGSO

Essential Targets Test code Test Indication
BRCA1, BRCA2, SMARCA4 M2.1 Known high grade serous ovarian carcinoma or In cases of diagnostic uncertainty of small cell carcinoma of the ovary
HRD status (either positive for BRCA 1 and/or 2, or HRD positive) M2.5 Patient is eligible for first line treatment and has a diagnosis of high grade ovarian cancer


Please note that SMARCA4 testing is not currently performed as part of this service.  Please contact your local genomics laboratory if there is a clinical requirement for SMARCA4 analysis.

Sample preparation is done in the local Cellular Pathology laboratory which holds the tumour blocks, and prepared under standardised molecular laboratory protocols, which include a clean molecular microtome and histopathologist training/quality assurance in marking up and assessing specimens for molecular testing. However, if your local Cellpath lab is unable to undertake this type of preparation, it would need to make contractual arrangements with another Cellpath lab in order to provide appropriate material to the Leeds Genomics Laboratory for genomic testing.

We request samples with >30% estimated tumour cell percentage: send one tube (Eppendorf or Universal) containing 5-10 x 10μm FFPE curls.

For samples with lower overall tumour percentage: if there is a region of the block with >30% tumour, please either:

a. macro dissect tumour-rich regions and send in a single tube (preferred), or;

b. send 10 x 5μm slide mounted sections along with marked H&E with tumour rich area(s) marked.

If it is not possible to macrodissect out a tumour rich region >30%, please contact the Leeds genomics laboratory for further guidance as to whether the sample can still be tested.

Curls should be cut under conditions that prevent cross contamination from other specimens. If using slide mounted sections, please clearly mark the slides with at least 2 patient identifiers. Cytology samples can be accepted for HRD and tBRCA testing. It is essential that cells and tissue fragments from the cytology samples are processed into agar/cell blocks, formalin-fixed and paraffin embedded. They should then undergo a Pathology assessment process as per tissue samples.

Requests for testing should be made via your local Cellular Pathology laboratory that holds the tumour tissue. Samples should be routed directly to your local Genomics Laboratory.

From April 2024, please use the GLH solid cancer referral form for all M2.5 and M2.1 testing requests. Please ensure that the referral form clearly specifies which tests are needed, gives tumour cell nuclei as a percent of nucleated cells (in macrodissected area if macrodissection used), and includes email addresses for emailing of results. Samples should be sent as soon as possible as the patient’s treatment might be dependent on the results of genetic analysis.

tBRCA sequencing and HRD testing will be undertaken by the Leeds Genomics Laboratory. Results will be reported by your local genomics laboratory.

Testing will be one of two options:

  1. M2.5 tBRCA and HRD testing. The GLH will assess HRD status and test for BRCA1 and BRCA2 sequence variants via the Illumina TSO500 HRD assay. Although the TSO500 HRD assay is a different assay, it uses the same Myriad Genomic Instability Score (GIS) algorithm for assessment of HRD status. This means that the clinical decision values displayed on the report remain unchanged.
  2. M2.1  tBRCA only testing. For those patients where only tBRCA is required, testing for BRCA1 and BRCA 2 variants will be undertaken using a customised next generation sequencing assay.

Pathway summary

Reports will include the following:

A clear statement on tBRCA and HRD status; implications and recommended action; and any recommendations for clinical genetics follow-up/ analysis of peripheral blood to confirm germline status/extended testing as appropriate.

If you have any questions about the specifics of testing, please get in touch with your relevant NEY GLH Genomics Laboratory below.

Newcastle Genetics Laboratory

Newcastle Genetics Laboratory
Central Parkway
Newcastle upon Tyne
Tyne and Wear

[email protected]


0191 241 8786

Sheffield Genetics Laboratory

Sheffield Diagnostic Genetics Service
Sheffield Children’s NHS Foundation Trust
Western Bank,
S10 2TH

[email protected]


0114 271 7014

Leeds Genetics Laboratory

Leeds Central Genetics Laboratory
Genomic Specimen Reception
Bexley Wing (Level 5)
St James’s University Hospital
Beckett Street

[email protected] or [email protected]


0113 206 5205