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Clinical guidelines - CUH WGS referrals

CUH clinician guidance for solid tumour Whole Genome Sequencing at East Genomics Laboratory Hub

  1. Eligibility for Whole Genome Sequencing (WGS)

Please see NHS England's test selection (opens in a new tab) or the national genomic test directory (opens in a new tab) for up to date guidance.

The commonest indications for WGS are currently:

  • Paediatric & Teenage/Young Adult (TYA) tumours (any tumour <25)
  • Sarcoma (any site, any age)
  • Triple negative breast cancer, glioma, and high grade ovarian carcinoma (any age)
  • Failed standard of care for treatment (i.e., refractory to current standard maximal treatment; any tumour type, including carcinoma of unknown primary, any age)
  • Failed standard of care for diagnostic testing (i.e., diagnosis not possible using non-WGS techniques; any tumour type, including carcinoma of unknown primary, any age)

The decision to proceed to WGS should ideally be made at MDT in conjunction with radiological, clinical and pathological input, but in certain situations it may be appropriate for the treating clinician to make this decision independently.

Further details on eligibility for molecular tests in cancer can be found in the National Genomic Test Directory.

When a decision has been made to proceed with WGS for a patient, please email the WGS fresh tissue co-ordinator with the patient details and (if known) the date and location (i.e., theatres, ultrasound, CT suite) of the procedure.

If the patient has also been consented for a trial involving tissue bank, the tissue bank team should also be informed.

2. Consent

An additional specialised consent process is required for WGS, particularly with reference to the implications of any germline variants that may be discovered.

Consent must be received prior to any biopsy of a tumour for WGS in which tissue (or extra tissue) is taken for the sole purpose of WGS.

The consent process requires completion of a training course “Patient Choice: Discussing Whole Genome Sequencing with Patients” (opens in a new tab).

Each patient’s (and family member where relevant) choices are captured via a nationally standardised Record of Discussion (RoD) form and additional forms where relevant. For WGS to be carried out a RoD must be available to the GLH (see below) for each individual undergoing WGS. The patient choice conversation can be performed remotely and the form submitted without a patient signature – please tick the “Remote consent” section of the RoD form to indicate this.

The completed and signed consent form (record of discussion) can either be e-mailed to the lab (with e-mail subject title “Cancer WGS consent”), posted to the lab with specimen (Cambridge Genomics Laboratory, Box 143), or uploaded to Media on EPIC.

3. Sampling the tumour tissue

Place an order on Epic for “Histopathology-Routine” for the biopsy.

In order to perform WGS, FRESH TISSUE IS REQUIRED.

This can be taken either:

1) as part of the diagnostic procedure up front (e.g., in paediatric, sarcoma or TYA cases)
2) as part of the treatment (e.g., in a diagnostic/therapeutic resection such as a hysterectomy), or
3) purely to obtain tissue for WGS (e.g., in a case where only formalin fixed tumour is currently available).

To perform WGS, an adequate quantity of tissue is required. To yield adequate quantities of DNA, the following guidelines are offered:

  • For core biopsies - tissue totalling ~40mm long (for 16g needle) or 80mm (18g)
  • For excisions/excisional biopsies - a fragment of tissue measuring 5 x 5 x 2mm

Please note that these are MINIMUM recommendations.

Please also bear in mind that these recommendations are purely for WGS, and that if routine histopathological diagnosis is also required, ADDITIONAL tissue should be taken for that purpose.

Further guidance on radiological biopsies is available in the dedicated document.

The specimen must be portered promptly to the main histopathology laboratory as soon as possible (ideally within 30 minutes), in chilled PBS (or similar isotonic solution) and handled by an appropriately trained laboratory staff member. If immediate transfer to the lab is not possible, the specimen can be kept at 4OC for a few hours whilst this is arranged.

If the specimen has been consented for sampling by Tissue Bank as part of a trial, the specimen should be sent to Tissue Bank on L5 of the laboratory block.

  1. Germline sample collection and requesting
Referral Volume of Blood Blood tube Preservative Type
Referral Adult Volume of Blood 3-5ml Blood tube Preservative Type EDTA
Referral Paediatric Volume of Blood >3ml Blood tube Preservative Type EDTA
Referral Infant Volume of Blood 1-3ml Blood tube Preservative Type EDTA

The preferred germline sample is peripheral blood. In exceptional circumstances, a saliva sample (using the Oragene collection tube) may be used as a source of germline DNA.

Detailed guidance on germline sampling is available via the FutureNHS (opens in a new tab) NHS Genomic Medicine Service workspace (see “GLH Sample Handling Guidance for Germline Samples”).

Internal CUH ordering for WGS is via Order Entry. The oncologist orders the germline sample, and the pathologist places the tumour sample order.

See appendices for EPIC ordering details

Appendix 1 - How to request the germline bloods in EPIC

Appendix 2 - Process of drive through/local blood collection

It is important to ensure that the correct orders are made, so the GLH have visibility of the sample and receive it via our pathway.

Please note, any haematological test directory indications should be ordered as a haem-onc WGS orders, even if the tumour tissue is sampled as a solid sample (i.e., histiocytosis and lymphoma).

5. Report and discussion at Genomic Tumour Advisory Board meeting (GTAB)

Genomics England stipulate that the results of WGS studies should be discussed at a GTAB.

A quorate GTAB will include an Oncologist, a Histopathologist, a Clinical Scientist and if applicable a Clinical Geneticist.

The GLH Clinical Scientist/Molecular Pathology team (which may be based at the Cambridge Hub or in some cases at your local centre) will present the findings to the GTAB colleagues for discussion.

Following the discussion, and the completion of any additional work (e.g., further characterization or confirmation using an orthogonal test of pertinent variants) a report will be issued.

Further information and guidance is available on our website.

Appendix 1: How to request the germline bloods in EPIC


The germline sample can be taken as an outpatient or inpatient.

Both the encounter type used, and the procedure version are key. If a germline specimen is not being collected during the inpatient encounter, then an outpatient encounter must be used e.g., Orders Only, and the outpatient version of the procedure/order must be used.

  1. Please place an order for Solid Cancer WGS Germline samples on EPIC via “Order Entry” > “Enter patient details” > “New”.
  2. In the pop-up box requiring “Type”, please write “Orders Only” then select “ADD ORDER” on the chart review page which appears.
  3. Type the Lab-code “LAB8591” for a Solid WGS Germline order.
  4. Please fill in all the details requested on EPIC with the symbol then sign orders.
  5. Go to Order enquiry > by patient (enter patient MRN)> Select your order and collect specimens> print labels.
  6. Please have one of your team take 5ml blood into an EDTA bottle and stick the EPIC labels on the EDTA tube.

For the Germline sample, please have the EDTA tube(s) portered to the GLH – for clarity, the address is below.

FAO: Solid cancer WGS team

East Genomic Laboratory Hub,
Box 143, Level 6 Addenbrooke's Treatment Centre,
Cambridge University Hospital NHS Foundation Trust,
Hills Road,
Cambridge, CB2 0QQ

It is important to ensure that the correct orders are made, so the GLH have visibility of the sample and receive it via our pathway.

Appendix 2: Process of drive through/local blood collection approach

Instructions for clinical team

  1. Place CANCER WGS GERMLINE order on Epic (via CUH)
  2. Print test request form via:
    1. Chart review (labs) > ‘Solid Cancer WGS Germline Sample’
    2. Order Requisition link (at bottom of WGS order)
  3. Tick DNA Tests: EDTA (FBC) tube box.
Solid Cancer WGS Germline Sample

4. Print Epic barcode label
5. Send both test request form + EPIC Label + EDTA tube to patient
6. Patient has blood taken at local hospital
7. Local hospital sends blood + test request form to GLH FAO: Solid cancer WGS team (Address/instructions/collection record all on test request form)

CUH WGS referrals flow chart
Figure 1: Summary Pathway for Clinician tumour WGS requesting (with colleague responsible and referenced guideline section)