CREATING POSSIBLE: MCRI BIOBANK FOR CELL-FREE DNA PROJECT UPDATE

By Dr Gabriel Dabscheck

Neurofibromatosis 1 (NFl) is an inherited genetic condition affecting one in 2500 people. Those with NF1 live 10 -15 years less than the general population, with the major cause of decreased life span being mortality related to malignant peripheral nerve sheath tumours (MPNSTs). MPNSTs are aggressive soft tissue malignancies or sarcomas that arise from plexiform neurofibromas.

Our study aims to identify and recruit eligible patients with NF1, to collect and store their serum samples in existing biobanks and keep a central database registry of those patients' clinical information, imaging data and biological sample location.

The registry will collect and store patient's samples over several years, at different time points. The purpose of this is to reflect the dynamic biology of plexiform neurofibromas. As plexiform neurofibromas grow, or become premalignant or malignant, they acquire mutations. This is a stepwise process that occurs over months and years. The purpose of collecting circulating tumour DNA over months and years it to capture this process.

We are delighted to have exceeded our initial goals for this project, in no small part thanks to the Children's Tumour Foundation. Your gift has meant we could establish a pilot and generate the necessary data to apply for and receive an MRFF grant to further our study.

Year 3 Update

With the support of the Children's Tumour Foundation (and thanks to Insitu Group's donation to the CTF) over the past three years, the funds helped to initiate the Biobank for Cell-free DNA project. With this, we were able to purchase necessary laboratory equipment such as the specialised Streck Cell-Free DNA BCT® tubes, laboratory consumables and service fees related to this study.

Since our last update, we have expanded to five sites, with active recruitment at:

• The Royal Children's Hospital 
• Royal Melbourne Hospital 
• Peter Maccallum Cancer Centre
• St Vincent's Hospital Melbourne
• Royal North Shore Hospital, NSW

In addition to these recruitment sites, we have also partnered with Advanced Molecular Laboratory at The Children's Hospital at Westmead, and the Garvan Institute in NSW.

We are very happy to report that as of February this year we have recruited more than 148 participants into our study and stored 338 blood samples (with more coming in). This is well ahead of targets to collect 250 blood samples by June 2023.

The Children's Tumour Foundation's gift meant we could purchase the necessary Streck Cell-Free DNA BCT® tubes to collect NF1 tumour samples in. These specific tubes contain a serum which means we can analyse the sample before it breaks down, as well as ensuring the integrity of the sample.

This collaborative multi-organisation study team is analysing and developing a liquid biopsy to identify MPNST's in people with NF1. The study team includes all the recruitment sites above as well as Dr Smadar Kahana- Edwin and Dr Leonard Goldstein from Westmead Children's and the Garvan Institute, who are developing a methylation based assay for detection of circulating tumour DNA signal of MPNST in serum of NFl patients.

Future Direction

Thanks to the support from the Children's Tumour Foundation, we have successfully set up and are actively recruiting into our NF1 biobank database. With the remaining time allocation of the MRFF grant, we will continue to collaborate our colleagues to achieve the goal of developing a liquid biopsy for identifying MPNST.

This biobank was set up to collect samples for future ethically approved research. Our biobank of samples and information will continue to be the most comprehensive database of its kind in the world for people who live with NF1.

The end of the MRFF grant period will deliver a validated and accurate liquid biopsy to diagnose MPNST in patients with NF1, ready for real-world roll-out and testing.

While a liquid biopsy has the potential to change the landscape of those living with a diagnosis of NFl, we still need to validate a screening program of MPNST in patients and proving that it leads to a decrease in mortality. This will involve additional work; it is essential to prove that such an approach is feasible before embarking on a larger project.

The Children's Tumour Foundation would like to also thank Insitu Group for their contribution to this project and for their ongoing support of the Foundation.