New research demonstrates the power of genome sequencing for understanding childhood cancer

Urological Malignancies programme member Dr. Tom Mitchell explains the groundbreaking findings in his recently published NEJM paper on childhood tumours.

Research published in the New England Journal of Medicine has demonstrated the power of genome sequencing to understand tumour development and inform clinical management. A team of scientists and clinicians from Cambridge and London studied somatic mutations in bilateral neuroblastoma.

Neuroblastoma is a common childhood cancer that can manifest as multiple tumours in both adrenal glands. Whether these come from the same ancestral clone, represent metastases or arise completely independently was unknown.

By comparing mutations acquired in the different tumours with blood of the same patient, it became apparent that each tumour shared mutations with blood not found in the other. This means that the tumours diverged very early in embryogenesis, within a few cell divisions after fertilization.

The tumours appeared to arise independently, but they evolved with remarkably parallel convergent events, mostly shaped by the inherited genetic mutation that predisposed them to cancer.

Importantly, using genome sequencing technologies, clinicians can then make the distinction between an aggressive tumour that had metastasised from one site to another, or more benign tumours that are localised and had arisen independently.

These lessons can be applied to other tumour types. Whereas bilateral adult tumours are less likely to have arisen independently, a significant proportion do. For instance, bilateral or multifocal adult renal cell tumours often have independent origins, and should be treated according to their individual pathological characteristics.

The presence of independent tumour formation should alert any clinician to the possibility of an inherited somatic mutation that could have laid the foundation of multiple tumour formation. In those cases, discussion surrounding the merits of genetic screening is recommended.

Read the full article in the New England Journal of Medicine.