The impact of genomics on pathology

For many years, genomic techniques such as gene panel testing and fluorescence in situ hybridisation (FISH) have been used to guide treatment decisions for cancer patients. Large-scale molecular studies have also identified new disease classifiers and highlighted the potential to gain prognostic and predictive information to influence patient management. Also, ‘mutational signatures’ or patterns of alterations across the genome have been identified for different cancer types, and some of these are being evaluated for their power to predict drug response and patient prognosis. Today the potential of the genomics revolution to transform personalised medicine is a focus of healthcare systems across the world, and the UK is leading the way with the 100,000 Genomes Project, as Dr Clare Craig and Professor Louise Jones explain.

Since its establishment in 2013, the 100,000 Genomes Project has driven the development of a genomic testing infrastructure for rare diseases and cancers within the NHS. Now, we are moving towards an era where genomic medicine becomes part of routine care – with the NHS in England offering a National Genomic Medicine Service from October 2018.

The NHS Genomic Medicine Service will rely on genomic multidisciplinary teams to interpret reports, of which pathologists will be key members, supported by genomic laboratories and IT infrastructure to integrate genomic testing into patient management, from diagnostics, through to treatment decisions based on a greater understanding of the molecular profile of tumours.

To fully embrace this era of genomic medicine, we know that pathologists will face the challenges that come with molecular diagnostics and whole-genome sequencing (WGS) in cancer. That is, the need to optimise and standardise handling tissue to achieve high-quality sequencing, while retaining morphology for diagnosis.

During the initial phases of the 100,000 Genomes Project, we carried out extensive experimental work to optimise and standardise the process of formalin fixation and to adapt the DNA extraction process to minimise DNA damage. While there was some improvement seen, WGS on formalin-fixed, paraffin wax-embedded (FFPE) tissue was found to be substantially suboptimal. This led to the conclusion that for optimal whole-genome sequencing, fresh tissue is required.

Collecting fresh tumour samples, however, presents its own difficulties. New laboratory processes must be introduced with care and due consideration for the impact on the wide variety of diagnostic tests performed on tissues. Pathologists around the country have risen to the challenge, from setting up systems to alert the laboratory that a fresh sample is imminent, to perfecting techniques for sampling small tumours without interfering with the histological diagnosis, and with several centres now trialling approaches such as vacuum-packing.

The health and safety concerns around formalin exposure are an additional motivation to remove formalin from theatres. Surgeons and nurses are helping to ensure that surgical resection samples can be refrigerated in theatres, with or without vacuum-packing, to allow for successful whole-genome sequencing. Thanks in large part to these pathologists sharing their knowledge and experience, there are now practical ways of collecting and sampling tissues for molecular diagnostics that overcome some of the problems with handling fresh tissue.

Owing to our work in the 100,000 Genomes Project, genomics has started to impact on pathology practice, but this is just the beginning. Working as part of a genomic multidisciplinary team, it is more important than ever for pathologists across the country to seize the moment and embrace genomic medicine – driving the best genomically-primed care for cancer patients.

Professor Louise Jones, Molecular Lead for Pathology

Dr Clare Craig, Clinical Lead for Cancer Recruitment

Genomics England



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