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General genomics

Dr Sarah Taylor, GatewayC GP Lead, speaks to Dr Fiona Lalloo, Consultant Clinical Geneticist, about cancer genetics.

Key points:

    • There are 2 types of genetic mutations:
      • Somatic mutations – these are mutations which are confined to the tumour and are useful to direct treatment 
      • Germline mutations – these are mutations which affect every cell in the body. This can affect treatment but can also cause a predisposition to malignancies for the patient and members of their family
    • Patients with germline mutations need referral to a genetics service. This is normally done by the oncology team, but primary care practitioners may be asked to refer family members
    • In that case it useful to know the name of the affected patient, the type of cancer and where they are being treated
    • Many cancers are environmental but 1-5% of cancers have a germline mutation
    • There are some cancer syndromes which have specific clusters of cancer types.

The National Genomic Test Directory lists the referral criteria for genetic testing for patients who are concerned about a family history of cancer

Factors which increase the probability of a germline mutation are:


  • cancers occurring at young age
  • individuals with more than one primary
  • clusters of cancer within a family

Many cancers are environmental, but 1-5% of cancers have a germline mutation.

There are some cancer syndromes which have specific clusters of cancer types.


Genomic testing in Wales

While the National Genomic Test Directory is owned, controlled and maintained by NHS England, the Welsh Health Specialised Services Committee (WHSSC) approve funding of genomic testing in line with the criteria identified in the Test Directory and implementation of these tests is being clinically prioritised in collaboration with a range of clinicians through the All Wales Medical Genomics Service.

Lung cancer

Lung cancer remains the main cause of cancer mortality in the UK, accounting for 21% of all cancer deaths. Smoking is the major risk factor for the development of lung cancer, however, a number of studies have found that in rare instances a family history may contribute to the development of the disease. 

Molecular testing to assess for somatic mutation is available to patients diagnosed with advanced stage Non-small cell lung cancer (NSCLC). There are targeted treatments for patient diagnosed with EGFR mutated; ALK or ROS1 rearranged NSCLC which can greatly improve outcomes. In addition there are multiple other mutations which may be investigated in individual patients.

Non-small cell lung cancer (NSCLC)

Any patients with adenocarcinoma are tested for the following somatic mutations:


EGFR mutation

ALK rearrangement

ROS1 rearrangement

Present in between 10-15% of patients with lung cancer.

More common in:

  • Women than men
  • Never/light smoking history
  • Younger adults
  • Asian descent

Present in around 3-5% of patients with lung cancer.

More common in:

  • Never/light smoking history
  • Younger adults

Present between 1 and 2% of patients with lung cancer.

More common in:

  • Never/light smoking history
  • Younger adults

Patients with a squamous cell carcinoma are far less likely to have a genomic mutation. However, based on individual cases typically with a never-smoking history, a tailored approach can be made to molecular testing.

For patients who have an actionable mutation, there are numerous lines of targeted therapies that can be given before standard chemotherapy or immunotherapy. Whereas, if screening results show that the patient does not have any actionable mutation, then the patient will be limited to chemotherapy +/- immunotherapy with an average poorer survival.

In EGFR mutation patients, the average survival is 2-3 years, increasing to 3-5 years in ALK rearranged patients. This has improved significantly over recent years with the development of targeted therapy with a tolerable toxicity profile.


Small-cell lung cancer (SCLC)

There is research on-going for mutations in SCLC, but there is currently no genetic screening taking place as stand of care.

Additional resources

Link: National Genomic Test Directory, NHS England
Link: All Wales Medical Genomics Service
Link: NCI Dictionary of Genetic Terms, National Cancer Institute
Link: Lung cancer mortality, Cancer Research UK (2020)
Link: Types of lung cancer, Roy Castle Lung Cancer Foundation
Link: Familial risk for lung cancer, Oncology Letters Vol 13:2 (2017)
Link: The Role of UK Oncogene-Focussed Patient Groups in Supporting and Educating Patients with Oncogene-Driven NSCLC, Oncology and Therapy (2021)
Link: Testing for gene mutations in lung cancer, Cancer Research UK (2019)
Link: Personalized, genotype-directed therapy for advanced non-small cell lung cancer, Lecia V Sequist and Joel W Neal (2021)
Link: Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer, Benjamin Solomon and Christine M Lovly (2021)
Link: Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, European Society for Medical Oncology (ESMO) (2020)

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