About the toolkit

From niche to necessity, genomic testing is now ready for rollout within the NHS. We want to help healthcare professionals deliver a gold standard of care to patients.

Genomics is rapidly becoming an integral part of cancer care and its clinical significance will only increase in time, transitioning into a central pillar of routine cancer treatment and prevention. Macmillan understands the importance of supporting both those living with and beyond cancer, but also the people who make that happen: the healthcare professionals.

This area of the toolkit will cover gynaecological cancers.

A headshot of Antigone Johnstone-Burt, Genomics Clinical Fellow at Macmillan. She is wearing a blue NHS uniform and her brown hair is tied back. She is smiling at the camera.

About the author

Mainstreaming criteria


These are the mainstreaming R207 panel inclusion criteria for inherited ovarian cancer (without breast cancer).

If a patient presents with one of the following, they are eligible for R207 panel testing.

  • High grade non mucinous epithelial ovarian cancer (EOC) at any age.
  • Epithelial ovarian cancer (EOC) AND:
    • 1 or more first degree relatives with EOC OR
    • 1 or more second degree relatives with EOC (where the separating relative has had a BSO, is male or is a deceased female). OR
    • 2 or more second/third degree relatives with EOC. 
  • Deceased affected individual where criteria above is met (or Manchester Score of 20) AND:
    • Appropriate tissue is available (tumour or normal) AND:
    • No living affected individual is available for genetic testing.

Further information about when to consider genomic testing (e.g. somatic testing) can be found on GeNotes.

Please refer to the National Genomic Test Directory for other tests related to Gynaecological Cancers.

Lynch (endometrial)

These are the R210 panel inclusion criteria for Inherited MMR deficiency.

All new diagnoses of colorectal and endometrial cancers should have tumour MSI/IHC testing completed. This may include BRAF testing in MLH1 deficient colorectal cancers and MLH1 hypermethylation testing in BRAF negative colorectal cancers and all MLH1 deficient uterine cancers.

MLH1 hypermethylation testing is included on the Cancer Test Directory under M1.5.

1. Criteria for germline testing an affected individual:

  • A dMMR tumour where additional testing results suggest Lynch Syndrome:
    • BRAF testing in MLH1 deficient colorectal cancers.
    • MLH1 hypermethylation testing in BRAF negative colorectal cancers.
    • ALL MLH1 deficient uterine cancers.
  • A positive family history of modified Amsterdam Criteria (regardless of dMMR tumour status).

Personal or family history suggestive of CMMRD (Constitutional Mismatch Repair Deficiency) with Wimmer score of 3 or more.

2. Criteria for MSI/IHC testing on a stored tumour sample prior to germline testing:

  • Personal/family history of colorectal cancers reaching Modified Amsterdam Criteria (≥ 3 cases of Lynch related cancer over ≥2 generations with ≥1 case diagnosed under 50yrs.
  • Any lynch-related cancer* (see below) under 50 years (excluding isolated pancreas, prostate or gastric cancers).
  • Two Lynch-related cancers (any age, if one is colorectal or endometrial).
  • Lynch-related cancer and 1 or more first degree relative has Lynch-related cancer (both occurred 60 years or less, one is colorectal or endometrial).
  • Lynch-related cancer and 2 or more relatives (first / second / third degree relatives) have Lynch-related cancer (all occurring ≤75years, one is colorectal or endometrial).
  • Lynch-related cancer and 3 or more relatives (first / second / third degree relatives) have Lynch-related cancer (occurring any age, one is colorectal or endometrial).

3. Criteria for somatic (tumour) Lynch syndrome panel testing:

  • Individual has colorectal or endometrial cancer with a dMMR tumour with normal BRAF and MLH1 hypermethylation analysis AND germline testing did not reveal a pathogenic mutation.
  • Personal/family pattern of disease whereby demonstration of acquired MMR mutations (and therefore exclusion of constitutional MMR abnormality) enables downscaling of surveillance
  • Deceased affected individual with colorectal or endometrial cancer ≤60 years AND tumour featuring high/intermediate MSI or loss of staining of MMR protein(s) on IHC, AND one first degree relative with Lynch-related cancer ≤60 AND no living affected individual is available for genetic testing.

4. Clinical Criteria for germline testing in an unaffected individual:

  • First degree relative affected with Lynch-related cancer, AND
  • Family history of colorectal cancer/Lynch-related cancers reaches Amsterdam Criteria (≥3 cases over ≥2 generations with ≥1 case affected <50 years) AND
  • Tumour sample analysis from affected family member has been attempted and is not possible, failed, indeterminate or indicates MMR deficiency (via IHC or MSI), AND
  • Somatic sequencing is not possible, or failed, AND
  • No living affected individual is available for genetic testing.

Testing of unaffected individuals can only be carried out by Clinical Genetics Services.

Please refer to the National Genomic Test Directory for other tests related to Colorectal Cancers.

*Lynch related cancers include:

  1. Colorectal cancer
  2. Endometrial cancer
  3. Epithelial ovarian cancer
  4. Ureteric cancer
  5. Transitional cell cancer of renal pelvis
  6. Cholangiocarcinoma
  7. Small bowel cancer
  8. Glioblastoma
  9. Endocervical cancer
  10. Multiple sebaceous tumours
  11. Prostate
  12. Gastric
  13. Pancreas

Preimplantation genetic testing is available to potential parents who are at risk of passing an inherited genetic condition down to their children. It is an IVF treatment that identifies the associated genetic change in embryos so that only the embryos that are clear of these pathogenic changes may be implanted. The process can take up to a year following initial consultation with a genetic counsellor.

Couples are eligible for treatment via the NHS if they meet certain criteria. Read more on the Genetic Alliance UK website.

Further reading

List of all inherited conditions that have been approved by the Human Fertilisation & Embryology Authority.

More detailed information on Preimplantation Genetic Testing for healthcare professional on NHS.UK

Patient pathways

Every unit will have variations on how patients navigate their pathway.

Please see below some examples of how genomic mainstreaming can fit into Secondary Care based on current clinical practice in NHS Hospitals.

Ovarian Cancer Pathway for Germline and Somatic Testing in Secondary Care [PDF]

Royal Marsden Partners have developed a Lynch Syndrome Early Diagnosis Pathway for Endometrial Cancer, showing how genomic mainstreaming can fit into Secondary Care based on current clinical practice in NHS Hospitals. Learn more about the project on the Royal Marsden Partners website.


  • Testing an asymptomatic adult who is related to a person with a diagnosed Lynch Syndrome pathogenic variant.
  • Not available to children, due to adult-onset disease associated with LS.


  • Testing of a patient’s germline to identify a pathogenic variant in one of the mismatch repair genes.
  • For all colorectal and endometrial cancer patients.
  • Follows an abnormal result from the test on tissue sample (abnormal MMR shown on IHC or MSI).
  • Offered to people with a history of LS tumours and a confirmed pathogenic variant in the family.


  • Aims to find relatives who carry a pathogenic variant for Lynch Syndrome before they develop a cancer.
  • In the UK, patients are relied upon to contact possibly affected relatives.
  • Georgiou et al, suggest a more novel approach of utilising healthcare providers, with patient consent to lead cascade testing.

Clinical Documents

NHS Genomic Medicine Service Test Order forms

Visit your region for local Non-Whole Genome Sequencing (WGS) form:

Referral forms

Each Trust will use their own documentation. See your local/nearest clinical genetics service for specific details of where to send your referral letter or form.

Letters of results

Educational resources for healthcare professionals

This section of the toolkit covers key points around counselling, consent and results. In addition, a list of frequently asked questions are answered.

Visit educational resources

Gynaecological Cancers Susceptibility Genes

This section of the toolkit covers the gynaecological cancer susceptibility genes:

  1. BRCA1 and BRCA2
  2. MLH1

  3. MSH2

  4. BRIP1

  5. MSH6

  6. PMS2

  7. RAD51C and RAD51D

Learn more about gynaecological cancer susceptibility genes

Clinic set-up and discussion tool

Most teams find that it takes around 3 months to set-up their services. This section of the toolkit provides some guidance to help think about what is needed during the set-up process.

Learn more about setting up a genomics service at your clinic

GMSA map

A map to highlight the boundaries when professionals are selecting their regional GMSA website.

Visit your regional Genomic Medicine Service Alliance (GMSA) website: