Epigenetic, Genomics, Pediatric Brain Tumors
Conditions
Brief summary
Central nervous system tumours are the most common solid tumours and the leading cause of cancer mortality in children, with high biological and prognostic heterogeneity. Despite advances in the 2021 WHO molecular classifications, treatment options remain limited and often ineffective in high-grade tumours. New third-generation sequencing technologies and three-dimensional models derived from patient tumours offer promising tools for more comprehensive genomic characterisation and preclinical evaluation of drug responses. However, the lack of integrated preclinical studies remains a limitation, necessitating coordinated projects to develop personalised therapeutic strategies. The study aims to investigate the genetic and biological characteristics of paediatric brain tumours. To this end, tumour tissue samples taken during planned surgery and peripheral blood samples will be analysed. Advanced genetic analyses will be performed on these materials to identify tumour alterations and the patient's genetic characteristics. In addition, experimental in vitro models derived from the tumour will be developed to evaluate the response to different chemotherapy drugs. The information obtained will be used to better understand the mechanisms of tumour growth and resistance and to promote the future development of more targeted and personalised therapies.
Interventions
DIAGNOSTIC_TESTGenomic DNA analysis of biological samples
Analysis of genomic DNA from tumor biopsy and blood samples
Sponsors
Meyer Children's Hospital IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 3-18 years with suspected brain tumours undergoing neurosurgery * No previous bone marrow transplants or other haematological procedures that could potentially interfere with germline analysis. * Patients who have not received any systemic anticancer treatment (including chemotherapy, radiotherapy or targeted therapies) prior to enrolment surgery. * Signature of informed consent
Exclusion criteria
* Subsequent histological confirmation of non-neoplastic brain pathology (e.g. malformations, inflammatory lesions, demyelinating processes). * Insufficient quantity or quality of tumour tissue or peripheral blood for the analyses required by the protocol. * Presence of serious clinical conditions, systemic infections or haemodynamic instability that contraindicate the collection of biological samples or inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Single Nucleotide Variants (SNV) | At enrollment and on the date of first documented progression assessed up to 12 months | Number of SNVs germline in DNA from tumor and blood samples |
| Number of copy number variations (CNVs) | At enrollment and on the date of first documented progression assessed up to 12 months | Number of copy number variations (CNVs) in DNA from tumor and blood samples |
| Number of triplet expansions | At enrollment and on the date of first documented progression assessed up to 12 months | Number of triplet expansions in DNA from tumor and blood samples |
| Number of structural variants (SVs) | At enrollment and on the date of first documented progression assessed up to 12 months | Number of structural variants (SVs) in DNA from tumor and blood sample |
| Morphological description of three-dimensional models derived from the tumour | At enrollment and on the date of first documented progression assessed up to 12 months | — |
| Vitality of three-dimensional models derived from the tumour | At enrollment and on the date of first documented progression assessed up to 12 months | — |
| Proliferative activity of three-dimensional models derived from the tumour | At enrollment and on the date of first documented progression assessed up to 12 months | — |
| Percentage of residual cell vitality after drug treatment | At enrollment and on the date of first documented progression assessed up to 12 months | — |
| Dose-response curves for each drug tested | At enrollment and on the date of first documented progression assessed up to 12 months | Ex vivo chemosensitivity study on three-dimensional models derived from primary tumour cells |
Countries
Italy
Contacts
CONTACTIacopo Sardi
Outcome results
None listed