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Genome sequencing accelerates cancer detection

last modified Sep 08, 2020 03:43 PM

Barrett's oesophagus and oesophageal cancer are diagnosed using biopsies, which look for signs of dysplasia. Between one and five people in every 100 with Barrett's oesophagus will go on to develop oesophageal cancer in their life-time, but as this type of cancer can be difficult to treat, particularly if not caught early enough, it is of immense benefit if the disease can be detected early.

But even as early diagnosis of cancer is one of the best strategies to improve patient survival and decrease the side-effects from treatments, this strategy can result in overtreatment – patients incorrectly identified as high-risk and given unnecessary treatments. Thus, new ways to accurately spot cancer progression at a very early stage to help identify those patients at greatest risk is a cardinal unmet need an issue addressed by this most recent paper from the Fitzgerald group.

A phenomenon commonly seen in the DNA of tumours – but not in healthy tissues – is one whereby whole ‘chunks’ of DNA are either deleted or repeated several times as cells copy and multiply. These are known as ‘copy number alterations’. In this latest study from the Fitzgerald group published today in Nature Medicine, researchers have shown how these copy number alterations could help diagnose patients earlier.

Using whole genome sequencing the team analysed 777 samples from 88 patients and compared their DNA against that from control samples collected during clinical surveillance for Barrett's oesophagus. They were looking for differences in the DNA between the patients who were eventually diagnosed with cancer versus those who were not.

It was found that the genomes in samples from individual patients who went on to develop cancer tended to have a higher number of copy number alterations, and that the number and complexity of such alterations increased over time. This information was used to develop a statistical model that could predict whether a patient was at a high or low risk of cancer from a single, tiny biopsy sample take

Relative Risk (RR) prediction across the cohort of samples – from Figure 2
n years before. The model was then used to predict and classify risks for individuals in a validation cohort of 76 patients and 213 samples.

The model accurately predicted oesophageal cancer eight years before diagnosis for half of all patients who went on to develop the disease. This increased to more than three-quarters of patients one to two years before a diagnosis.

Equally importantly, the model accurately and consistently predicted patients who were at a low risk of developing cancer over many years of clinical surveillance. This meant that these patients did not need to be subjected to regular, invasive monitoring or treatment.

A high degree of variability in copy number alternations was found even within a single biopsy, but even so, the model provided surprisingly stable predictions of a patient’s risk of progression to cancer.



Killcoyne, S. et al. 
Genomic copy number predicts esophageal cancer years before transformation. Nat Med; 7 Sept 2020; DOI: 10.1038/s41591-020-1033-y