The study, published in Nature and part-funded by The Brain Tumour Charity’s Future Leaders programme, investigated the origin of group 3 and 4 medulloblastoma in the developing human cerebellum, finding that these tumour subtypes both originate in the rhombic lip.
What is the rhombic lip?
The rhombic lip is a part of the embryonic brain. It contributes to the development of the cerebellum (responsible for movement and balance).
The landmark findings greatly enhance our understanding of the causes of these tumour subtypes. This could help scientists discover new and kinder treatments that could target these different cell types.
Medulloblastoma: one of the most common high-grade brain tumours in children
Medulloblastoma is most often found in the cerebellum. It is a common high-grade brain tumour in children. Around 55 children are diagnosed each year in the UK.
There are four different subgroups of medulloblastoma (WNT, SHH, group 3 and group 4). They are classified according to their genetic profiles. Group 3 and 4 account for approximately 65% of diagnosed tumours.
The origins of the WNT and SHH subgroups have already been discovered. However, understanding the origins of group 3 and 4 medulloblastoma has been more difficult.
Uncovering the origins of medulloblastoma
Researchers including Dr Laure Bihannic at St. Jude Children’s Research Hospital, who is funded by The Charity, investigated the genetic mutations in group 3 and 4 medulloblastoma samples. Their aim – to identify the similarities and differences between the subgroups.
Genes important in both subgroups were investigated and found to be associated with the human foetal rhombic lip. This provided further evidence of their related origin.
Researchers also explored the location of small medulloblastoma in patients. They hoped that examining these tumours in their early stages may confirm their previous finding about their origin.
Analysis of MRI scans showed that both tumour subtypes shared a common location of the nodulus and fourth ventricle. This further supported the rhombic lip origin of these tumour subtypes as this location contains the residual rhombic lip in a developed brain.
Improving treatment accuracy
This in-depth understanding of tumour origin and location could enable specialists to improve the accuracy of treatment for group 3 and 4 tumours. And aims to preserve the surrounding healthy tissue. This could help reduce the side-effects for children undergoing treatment and help to protect their quality of life.
The research was led by scientists at St. Jude Children’s Research Hospital and the University of Washington in the USA, with collaborating sites that included the Institute of Genetic Medicine at Newcastle University and Great Ormond Street Hospital for Children in the UK.
These findings replace the long-standing view that group 3 and 4 medulloblastoma represent entirely different diseases. And with this more accurate understanding will come more accurate treatment.
In parallel research, scientists in the USA and Canada have independently confirmed that group 3 and 4 medulloblastoma originate in the rhombic lip. They also showed that these cells appear to be ‘stalled’ in their development at birth which opens unique opportunities for early monitoring and treatment to prevent group 3 and 4 medulloblastoma.
Research such as this could provide the basis to better understand the origin of other childhood cancers during embryo development, offering opportunities for early detection and prevention.
Dr Laure Bihannic, one of The Brain Tumour Charity’s Future Leaders, based at St Jude Children’s Research Hospital said:
“This research has enhanced our knowledge of medulloblastoma and has changed our understanding of group 3 and 4 subgroups. Understanding the origin of these tumours will improve treatment, and allow researchers to develop novel and more specific drugs based on the genetic markers of the different tumour subtypes. We are hopeful that these insights will help clinicians deliver more precise treatments by focussing on the origin of the tumour, thus reducing damage to healthy tissues.
“The support from the Brain Tumour Charity’s Future Leaders programme has allowed us to dive deeper into the origins of one of the most common paediatric brain tumours which will help pave the way for new treatments in the future.”
Dr David Jenkinson, Chief Scientific Officer at The Brain Tumour Charity, which helped fund the study, said:
“This study changes what we know about group 3 and 4 medulloblastoma and this is a really positive step to understanding more about this type of tumour in children, and brings us closer to developing novel treatments.
“Over 65% of medulloblastoma diagnoses in children are group 3 or 4 tumours, and understanding their development and genetic hallmarks will open doors for new drug discovery. This is particularly important as effective targeted therapies are largely non-existent.
“This research was supported by the Charity’s Future Leaders programme, funding the very best early career scientists and their research to help them establish their careers in neuro-oncology and to help us achieve our aims of doubling the survival of those diagnosed and halving the harm they cause. We are proud to have been able to support such pioneering work.”