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ctDNA and metabolites in CSF serve as novel biomarkers for CNS germ cell tumours

Researchers have validated the use of circulating tumour DNA (ctDNA) and metabolites in cerebrospinal fluid (CSF) as potential biomarkers for central nervous system (CNS) germ cell tumours (GCTs).

Germ cell tumours

GCTs in the CNS are extremely rare. They make up less than 3% of primary brain tumours. However, the incidence of these tumours differs among races, with a higher incidence in Asian individuals than in White individuals. Males are also disproportionately affected, with a male to female ratio greater than 3:1. In addition, GCTs in the CNS predominantly occur in children and adolescents. The most common type of GCT is germinoma, which is highly radiosensitive. A recent study showed that the 5-year survival rate of germinoma exceeded 99%. However, non-germinomatous GCTs (NGGCTs) require intense chemotherapy, irradiation and sometimes surgical resection. The prognosis is also less favourable with a 5-year survival rate of 71.4–87.3%. Therefore, distinguishing between these tumour types is critical in determining the appropriate treatment strategy.

Biomarkers currently used in the clinical management of CNS GCTs include serum and CSF levels of α-fetoprotein (AFP), β-subunit of human chorionic gonadotropin (β-HCG) and placental alkaline phosphatase (PLAP). Biopsy samples for histological analysis are often small and only reflect a specific region of the tumour. This sampling bias leads to inaccuracies in histologic diagnosis. This also makes it challenging to distinguish between pure germinoma and NGGCT, as NGGCT samples can contain germinoma components. Whilst oncologists manage both these patient groups with chemotherapy and radiotherapy, therapeutic regimens such as radiation dose differ. As a result, additional biomarkers must be identified for an accurate distinction between germinoma and NGGCTs to be made.

Analysis of ctDNA and metabolites

In this study, published in Scientific Reports, researchers analysed both ctDNA and metabolites in CSF from patients with CNS GCTs. They investigated CSF samples from 12 patients with CNS GCTs – 8 germinomas and 4 NGGCTs. The aim was to identify biomarkers that may have potential clinical utility.

The team were able to detect KIT and/or NRAS mutations in 25% of patients. These genes are frequently mutated in GCTs. They also found significant differences between control and GCT samples in the abundance of 15 metabolites. In GCTs, metabolites associated with the TCA cycle increased, while urea, ornithine, and short-chain acylcarnitines decreased. This reflects disruption to key metabolic pathways. In addition, they found differences in abundance of several metabolites in patients with germinomas and NGGCTs.

These results suggest that ctDNA and metabolites in CSF could serve as novel biomarkers for CNS GCTs. These biomarkers may also be useful in distinguishing between germinomas and NGGCTs. The team believe that healthcare professionals could use such biomarkers to monitor patients, following initial treatment.

Image credit: By Image Team –

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Biomarkers / CNS / ctDNA / Tumour