Neuroblastoma stage 3 and 4 is a chemotherapy-resistant, highly aggressive disease. High-risk neuroblastoma frequently displays gene defects which fall in three almost non-ovelapping categories. With the use of whole-genome sequencing studies, one of these three groups has been identified as patients with genomic rearrangements associated with an increased expression of a gene called TERT and poor outcome.
It is essential that methodologies allowing routine detection of TERT rearrangements in parallel with other commonly found genetic alterations are integrated into upcoming clinical trials in order to better characterise these distinct groups within clinical trial datasets.
Early Detection
A major clinical application of the early detection of TERT rearrangements would be to help categorize cases and treat accordingly, i.e since these tumors usually show progression and recurrence complete resection is usually considered, even in infant cases.
Samples From Children
The Paediatric Solid Tumour Panel has been offering Next Generation Sequencing (NGS) with clinical reporting to children with sold tumours since March 2016. In March 2017 the Panel was updated in order to capture TERT rearrangements and is currently being validated using a cohort of patient samples for the detection of TERT rearrangements in high-risk neuroblastoma cases. So far, more than 150 samples from children with solid tumours in the UK, of which 20 had a diagnosis of neuroblastoma, have been successfully NGS panel sequenced and clinically reported.
Clinical Trials
Incorporating prospective molecular data collection into upcoming clinical trial datasets will enable a greater understanding of genotype-phenotype correlation, leading to more accurate risk stratification and better, more tailored therapies in the future. Clinical NGS panel sequencing is feasible, can detect complex rearrangements in addition to other genetic alterations and can be tailored to the needs of the study population.
