Genomic medicine strategy 2024 to 2029

8. Clinical priorities

While the potential for genomic medicine is vast, the focus of this strategy is on cancer and rare and inherited conditions. These represent both areas of immediate need and provide opportunities to develop partnerships and delivery models that can be expanded and built upon beyond the terms of this strategy.

Rare conditions are defined by the UK Rare Diseases Framework as those affecting no more than 1 person per 2,000.^[9] Although individually rare they are collectively common, with an estimated 1 in 17 people in the UK affected by a rare disease at some point in their lives.^[9] While not all rare conditions are genetic, the vast majority (an estimated 80%) have a genetic origin.^[10] Cancer, a disease of the genome, is caused when changes in a person’s DNA cause cells to grow and divide uncontrollably. These changes can be inherited through families (known as ‘germline’ variants) which account for around 5-10% of cancer, or they can be acquired during a person’s lifetime (known as ‘somatic variants’). Both germline and somatic variants may influence how a person’s cancer behaves or responds to treatment. Cancer can be further split into solid tumour (an abnormal clump of cells that does not contain any liquid or cysts) and haematological malignancies (cancers of the blood, bone marrow and lymph nodes). While cancer is very common in Scotland, there are many different types of cancer which on their own are considered to be rare (defined as an incidence of 6 per 100,000 people). As with rare conditions, rare cancers collectively account for more than 22% of all cancer diagnoses.^[11] There are, therefore, many interdependencies and interactions across the testing, clinical pathways and services for people with cancer and with rare and inherited conditions, and many opportunities for shared learning and knowledge exchange.

Cancer genomics

As set out in the recent Cancer Strategy for Scotland 2023 to 2033, cancer is one of Scotland’s biggest health challenges. Improved understanding of cancer genomics has resulted in a requirement for genomic testing to help inform diagnosis and determine the most effective clinical management.^[12]

In a number of cancers, specific genetic alterations are indicators of response or resistance to cancer therapies, as well as being useful for disease monitoring and risk assessment of disease recurrence. Due to the growth in development of targeted therapies (those where a genetic marker determines benefit) there is a consequential requirement for genomic information to determine eligibility and patient selection for many clinical trials.

Based on the current trajectory, genomic testing and the use of genomic information is expected to become central to cancer diagnostics within the next 10-20 years.^[13] For people with rare cancers and cancers that are more difficult to diagnose and treat, access to genomic information and expanded access to biomarker testing can be transformative in enabling people to benefit from precision therapies and management. The current use of genomic testing within teenage and young cancer (TYA) cancers and paediatric cancer as set out in Case Study 9.1. illustrates the value that genomic medicine already has, and how it is predicted to transform cancer care and management.

8.1. Case study: The application of genomic medicine in Teenage and Young Adult (TYA) and Paediatric cancer care

Diagnostics in haematology and oncology is an ever-expanding field, with new technologies being developed and implemented in clinical decision making at an extraordinary rate. Within the paediatric and young adult populations, the addition of NGS, RNA sequencing and whole genome sequencing (WGS) is changing how we predict the course of a disease (prognosis) and the likely outcomes for people affected by different types of cancer and shape decisions about how to best manage care and treatment.

A good example of this is a 9-year-old male who presented to his GP with a 1-week history of easy bruising and intermittent fevers. Blood tests demonstrated a high white cell count and he was diagnosed with acute myeloid leukaemia (AML). AML is a cancer of the blood and bone marrow that requires urgent treatment, or the patient will die. Genomics is used routinely within AML to determine disease risk and outcome upfront, as well as guide treatment decisions depending on different genetic abnormalities. This 9-year-old patient had a specific genetic abnormality associated with a more low-risk disease and he was treated in accordance with best practice. As he was diagnosed in England, WGS was performed at diagnosis and this demonstrated that, along with the genetic abnormality, he had a mutation (a variation) within a specific gene, termed cKIT. Mutations of cKIT are found in up to 50% of patients with specific genetic abnormalities and are thought to be associated with poorer patient outcomes and often a poorer response to treatment. In keeping with this, our patient had detectable disease after initial treatment and required a stem cell transplant. Following transplant, clinicians looked at his bloods and were concerned that there was a risk of disease relapse (the disease coming back). The clinicians used NGS to track the genetic abnormality and the cKIT mutation to ensure that this was not the case and he continues to be followed up by paediatric haematology services. If there had been a disease relapse with a cKIT mutation identified, a targeted treatment would have been used to give him the best possible chance of recovery. This highlights the use of genomics in assessing disease development and treatment response, and allows the potential use of new targeted, personalised treatments.

Rare and Inherited Disease conditions

Scotland’s first Rare Disease Action Plan, published in December 2022, set out the priorities for improvement identified by engagement with the rare disease community in Scotland. We will work closely with Scotland’s Rare Disease Implementation Board (RDIB) to ensure alignment between their aims and actions and those set out in this strategy.^[14]

An accurate diagnosis from genomic testing can lead to better management of a rare and inherited condition, access to therapies or avoidance of unnecessary therapies and improved quality of life. The ‘diagnostic odyssey’, the time that people with rare genetic conditions can wait for a diagnosis, can vary from months to decades.

This can have a considerable impact in terms of the time and expense involved in extensive rounds of investigation, the available options in terms of care and management and emotional distress for both patients and their families.^[15] Understanding the underlying genetic cause, and whether a condition can be inherited, allows people to consider their options around family planning, while being able to name a condition opens up potential access to support communities and resources. Within maternal and foetal medicine, genomic testing is also increasingly used to guide the diagnosis and assessment of a range of different congenital conditions, helping to guide decision-making on pregnancy, antenatal and postnatal management and family planning.

Beyond the benefit for expectant families and unborn children, genomic testing is an essential part of providing a diagnosis for children with developmental disorders and other serious genetic conditions, providing important information for their parents as to causation and prognosis. In some situations, this is required urgently in order to deliver the best possible care and improve people’s health outcomes. Genomic information increasingly now leads to changes in treatment. Many adults also have genetic conditions where correct diagnosis and management has a key impact on health, including in inherited heart disease, cancer risk and metabolic disorders.