Genomics toolkit: Lung

This area of the toolkit will cover lung cancer types.
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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. 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 lung cancers.

About the author

Dany Bell is a Strategic Adviser Treatment, New medicines, Genomics at Macmillan Cancer Support.

Learn more about Dany's work.

Mainstreaming criteria

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 patients 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.

Somatic genomic testing

Somatic gene variants (mutations) found in lung cancer include EGFR, ALK, MET, ROS1, BRAF, RET, KRAS, NTRK, PD-L1 and HER2. Tissue biopsies are the only way to confirm a diagnosis and detect driver mutations. However, under certain circumstances, liquid biopsies done on a sample of blood may be an option.

Non-small cell lung cancer (NSCLC) somatic eligibility criteria includes:

  • Multitarget NGS panel small variant – EGFR, ALK, BRAF, KRAS, MET

    All NSCLC eligible, with selected squamous cell with clinical features consistent with higher likelihood of a targeted mutation – e.g., non-smokers younger than 50 years old.

  • Multitarget panel with structural variant – ROS1, RET, EML4-ALK, NTRK1, NTRK2, NTRK3, MET

    All NSCLC eligible, with selected squamous cell with clinical features consistent with higher likelihood of a targeted mutation – e.g., non-smokers younger than 50 years old.

  • Multitarget NGS panel – MET

    If molecular assessment will aid diagnosis or management.

  • EGFR hotspot tumour

    All NSCLC eligible, with selected squamous cell with clinical features consistent with higher likelihood of a targeted mutation – e.g., non-smokers younger than 50 years old.

  • EGFR hotspot ctDNA

    If biopsy unavailable and detecting EGFR in ctDNA if patient eligible for tyrosine kinase inhibitor.

  • RS01 rearrangement

    If molecular assessment will aid diagnosis or management.

  • RET rearrangement

    If molecular assessment will aid diagnosis or management.

  • MET copy

    Where knowledge of ALK mutations would alter management.

  • EML4-ALK
    • All NSCLC eligible, with selected squamous cell with clinical features consistent with higher likelihood of a targeted mutation – e.g., non-smokers younger than 50 years old.
    • Eligible for tyrosine kinase inhibitor therapy.
  • ALK hotspot ctDNA
    • All NSCLC eligible, with selected squamous cell with clinical features consistent with higher likelihood of a targeted mutation – e.g., non-smokers younger than 50 years old.
    • Where knowledge of ALK mutations would alter management.

Small cell lung cancer (M321) somatic eligibility criteria:

  • Multitarget NGS panel RB1

    When making a diagnosis not possible via routine morphological or radiological criteria.

  • Multitarget panel NTRK1, NTRK2, NTRK3

    Clinical status means eligible for NTRK inhibitor if NTRK variation detected.

Mesothelioma (M5) somatic eligibility criteria:

  • CDKN2A

    Diagnostic uncertainty re mesothelioma or benign or reactive mesothelial proliferations.

  • Multitarget NGS panel NTRK1, NTRK2, NTRK3

    Clinical status means eligible for NTRK inhibitor if NTRK variation detected.

  • Multitarget NGS panel (CDKN2A)

    Diagnostic uncertainty re mesothelioma or benign or reactive mesothelial proliferations.

Other somatic markers

  • PDL
  • TMB
  • HER2

National directories

This is a changing list as new mutations and treatments are still being discovered, so check relevant test directory for updates regularly (at least annually).

Germline genomic testing

Only about 8% of lung cancers run in families. For people who have two or more first-degree relatives (brothers, sisters, parents or children) who developed lung cancer, the chances of developing lung cancer are even higher.

However, there is currently no formal indication for germline genomic testing for patients with lung cancer.

Pathogenic germline variants in epidermal growth factor receptor (EGFR) have been reported in small numbers in families so there is no NHS funding to test for this.

Lung adenocarcinoma of the lung, particularly broncho-alveolar subtypes at a young age are the most common inherited lung cancer and could be part of the cancer predisposition Li-Fraumeni Syndrome caused by germline variants in TP53.

So lung cancer patients at a young age should be asked about family history of Li-Fraumeni related cancers – soft tissue sarcoma, adrenocortical carcinoma, choroid plexus cancer, premenopausal breast cancer, brain cancer and childhood cancer. Those meeting the Chompret criteria may be eligible for genomic testing of the TP53 gene after appropriate counselling.

Some researchers suggest that there is an increased lung cancer risk in those with pathogenic variants in BRCA2 or other cancer susceptibility genes, but further data is required to clarify disease association.

Whilst somatic testing in lung cancer is well established the inherited component to lung cancer is less well understood and complex.

For more information about inherited cancer risk see the national directory for rare and inherited disease.

Patient pathways

There may be local variation, but ideally standardised where available (NICE).

Patients are tested at diagnosis:

  • Stage 1B-3A EGFR on resected tissue
  • Stage 1B-3A PDL-1 on resected tissue
  • Metastatic disease – comprehensive panel testing.

At disease progression:

  • To check for treatment resistance. For example, EGFR resistance mechanisms that are targetable T790M
  • To check for other biomarkers – mostly for clinical trials
  • Patient by patient basis.

Find out more: Wales lung cancer biomarker testing pathway (see page 5).

Clinical documents

NHS Genomic Medicine Service test order forms

Local genome sequencing forms:

Results guidance and information on somatic testing

If a somatic (tumour) driver mutation is identified in an individual with lung cancer, it may have implications for the choice of treatment for their current cancer. For more on this, see GeNotes ‘In the Clinic’ articles on the following results scenarios:

Patient with mesothelioma and somatic (tumour) NTRK rearrangement.

See our example of a request form. These may be different by GMSA so check your GMSA for more information.

Patient information and support

Educational resources

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

Lung cancer and somatic variants

Somatic variants are genetic changes that occur in cells of the body after conception. They are not inherited. In lung cancer, somatic variants are present in certain cells of the lung and are acquired during a person's lifetime.

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.

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:

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