Tumor DNA from medulloblastoma is present in large quantities in the cerebrospinal fluid and can be used to accurately diagnose and monitor cancer progression, show Spanish study findings.
“By evidencing the promise of cerebrospinal fluid as liquid biopsy for the personalized treatment of this extremely aggressive disease, our findings could ultimately spur the development of more effective and tailored therapeutic strategies,” says Joan Seoane, Ph.D., a senior researcher and professor based jointly at the Autonomous University of Barcelona and Vall d’Hebron University Hospital, who led the research.
“As importantly, they could also reduce excessive treatment to prevent long-term secondary effects,” he adds.
Medulloblastoma is the most common childhood brain cancer. It can be very treatable, but there are several different types of this cancer of differing severities, making it important to make an accurate diagnosis to give patients the best treatment and chance of survival.
Accurate diagnosis of brain tumors via tissue biopsy can be tricky, due to the location of the tumors. Traditionally, medulloblastoma has been first treated by surgical removal of the tumor, when tissue biopsy samples are taken for diagnosis. But these can be unsatisfactory, with insufficient sample sizes, presence of non-tumor tissue and tissue artefacts all causing problems.
To assess the accuracy of the cerebrospinal fluid “liquid biopsy,” Seone and colleagues collected blood, tumor and cerebrospinal fluid samples from 13 patients ranging in age from less than 1 year to 14 years and analyzed them using PCR techniques used for blood-based liquid biopsies.
They found that although circulating tumor DNA was not present in high levels in the blood, it was abundant in the cerebrospinal fluid and gave an accurate representation of the subtype of tumor and its degree of cellular heterogeneity.
This information can be very useful for oncologists who are trying to decide the best treatment for their patients. For example, medulloblastoma tumors with mutations in the PTCH1 gene can respond well to drugs that inhibit the Hedgehog signalling pathway. It could also be used to monitor the progression of the cancer or effectiveness of treatment in a less invasive way.
“Medulloblastoma is highly a complex, heterogenous tumor type that evolves over time. Currently, acquiring further samples to monitor and track changes in the tumor to more precisely match the most effective therapy in real time represents a major challenge. By liquid biopsy of cerebrospinal fluid, we aim to respond to the critical need of rendering the molecular characterization and monitoring of this disease more precise,” says Laura Escudero, Ph.D., a researcher working with Seoane and first author of the Nature Communications paper describing the work
“Larger cohort studies are now warranted to bring cerebrospinal fluid as liquid biopsy closer to the clinic and deliver on the promise of precision medicine for the treatment of this disease,” concludes Seoane.
