Genomics in Oncology

If you need an introduction to genomics in cancer care, watch our short explainer film below.

While genetics looks at individual genes, genomics refers to the study of all of a person’s or organism’s DNA and it can provide a more comprehensive view of health and disease.

Rapid advances in our knowledge and the increased availability and affordability of tests mean that genomics is increasingly important and relevant within specialist clinics.

Genomic data is increasingly used in the clinic to inform diagnosis, risk stratification, and treatment selection.

If you are new to oncology and would like to understand how genomics is used in cancer care, you can watch this short explainer.

Advances in genomic technologies and our understanding of genomics are changing the way we care for patients and families affected by cancer. 

Genomics can be used in two ways in cancer care as we are dealing with two different genomes:

  1. First there’s the genome of the patient. Some changes in this genome - known as ‘germline variants’ or ‘germline mutations’- can make an individual more susceptible to cancer. For example, a variation in the BRCA1 gene, which plays a role in DNA repair, significantly increases the risk of breast cancer.
  2. Second, there’s the genome of the cancer. The majority of cancers are not due to an underlying, inherited predisposition, but are caused by spontaneous changes that occur in an individual cell. Spontaneous changes within a cell’s DNA are known as ‘somatic variants’, ‘somatic mutations’, ‘acquired variants’ or ‘acquired mutations’, and some of them can lead to cancer. Experts can analyse these changes in cancer cells to provide a molecular diagnosis that can in many cases be used to guide treatment and management. For example, identification of an EGFR mutation in tumour cells increases the chances of a lung cancer responding to a drug called gefitinib.

Advances in next generation sequencing mean that we can now test more genes concurrently and access results rapidly, meaning they can be used to inform treatment; there is a need for all oncologists to be up to date with genomics as testing is increasingly part of the diagnostic pathway.

High penetrance mutations in cancer susceptibility genes underlie a number of cases of cancer. For example, over 40% in malignant paraganglioma, 15-20% in ovarian cancer and 5% in breast and colorectal cancers.

Most mutations in cancer susceptibility genes are autosomal dominant in their inheritance. Our understanding of the penetrance of specific cancer susceptibility genes and mutations is evolving: we are aware that some of the figures used historically may be inflated on account of being derived from the very large families in which these gene mutations were first identified and studied (ascertainment bias).

Early identification of those with increased cancer susceptibility is important because it offers opportunities for intervention, for example:

  • prophylactic surgery, for example salpingo-oopherectomy (BRCA), mastectomy (BRCA, TP53), gastrectomy (CDH1), colectomy (APC);
  • chemoprevention, for example aspirin (MMR-deficiency), tamoxifen (BRCA2);
  • intensive surveillance, for example annual MRI scans for breast cancer (BRCA, TP53); and
  • modification of lifestyle/non-genetic factors.

It is important that all oncologists, and not just clinical geneticists, consider whether the pattern of cancer in the patient +/- their family suggests underlying genetic susceptibility and enact evaluation and/or referral for genetic testing.

Analysing the DNA of a tumour provides opportunities to target treatment in several types of cancer, with potential to both improve response and avoid harmful side effects. For example, knowledge of an underlying germline mutation in a BRCA1/2 gene can inform oncologists’ choice of drug treatments for those with breast and ovarian cancer.

The quality of genomic data has been found to be much improved if DNA is extracted from fresh-frozen (rather than FFPE) tumour samples, which has implications for all clinicians and scientists involved in tissue collection.

Advances in molecular technology mean that it is now feasible to obtain the entire sequence of DNA of a cancer cell within a few days and at an achievable cost. Panel tests allow us to test a number of genes concurrently. In addition to looking for individual gene mutations which can predict whether a patient is likely to respond to a targeted therapy, we can also look at the overall pattern of mutations in a cell which can give us important information about the underlying biology of the cancer.

We have now seen the advent of technologies that can detect circulating tumour DNA for some cancer types. This can be used to identify potential targets for treatment, for example EGFR mutation status in non-small cell lung cancer. Research suggests that this may offer the potential to monitor some individuals for cancer recurrence.

Clinical trials of new targeted anti-cancer drugs are increasingly being designed so that they are open to patients with a range of different tumour types which share specific DNA mutation profiles, instead of just one tumour type.

Colorectal cancer and Lynch syndrome

  • Patient is a woman diagnosed with right-sided cancer of the colon aged 53
  • On account of new NICE guidance, all colorectal cancers are eligible for tumour testing for mismatch repair (MMR) deficiency (immunohistochemical staining and/or microsatellite instability testing)
  • Absence of immunohistochemical staining for MSH2 and MSH6 is shown for her tumour. It is also shown to be microsatellite unstable at 6/6 markers.
  • Following these findings, she is referred to clinical genetics and testing is performed for a panel of genes associated with MMR (MLH1, MSH2, MSH6, PMS2). She is found to have a pathogenic variant (mutation): MSH2 c.1046C>T p.(Pro349Leu). Whilst not a classical ‘protein-truncating’ mutation, this missense variant has been classified as pathogenic by the INSIGHT ( expert group on the ClinVar online resource (
  • On account of her status of having a germline MSH2 mutation.
    • her adjuvant chemotherapy is amended to exclude 5-FU/capecitabine, which are not effective in MMR-deficient tumours; and
    • rather than a bowel resection, a sub-total colectomy with ileosigmoidal anastomosis is performed to reduce her risk of future colorectal cancer.
  • She is enrolled in a trial of anti-PD1 drug (ipilimumab) for adjuvant treatment of her tumour. These drugs are licensed and approved for metastatic cancer which shows microsatellite instability; trials examining benefit in the adjuvant setting are underway.
  • She is subsequently enrolled on the CAPP3 study ( . Aspirin has been demonstrated to reduce risk of colorectal cancer in individuals with MMR gene mutations (Lynch syndrome). The CAPP3 study is exploring the optimal dose of aspirin when used in this setting for chemoprophylaxis.
  • Once recovered from her colorectal surgery, she undergoes risk-reducing hysterectomy and bilateral salpingo-oopherectomy to reduce the risks of endometrial and ovarian cancers associated with the MSH2 mutation.
  • Family members are invited for predictive testing for the MSH2 mutation. Those found to carry it are offered intensive colorectal surveillance (colonoscopy every 18 months from age 25) as well as gynecological risk-reducing surgery.