Clinical guidelines - CUH WGS referrals

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.

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.

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 4^OC 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.

The preferred germline sample is peripheral blood. Required volumes are indicated in the table below. 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).

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.