Cerebrospinal fluid as liquid biopsy for characterizing and policing of medulloblastoma

Joan Seoane, Director of Translational Research, Vall d’Hebron Institute of Oncology (VHIO). Photo credit: VHIO

Building on previous research 1-3 conducted by Joan Seoane, Director of Translational Research at the Vall d’Hebron Institute of Oncology (VHIO) and ICREA Research Professor, the latest results from a proof-of-concept study published in Nature Communications show This analysis of the circulating tumor DNA (ctDNA) of the cerebrospinal fluid (CSF) enables more accurate characterization, molecular diagnosis (including subtyping and risk stratification) and real-time tracking of medulloblastoma (MB) – the most common malignant brain tumor in childhood.

The results, which were carried out in multidisciplinary collaboration on the campus of the Vall d’Hebron Barcelona Hospital, also demonstrate that this novel and less invasive approach can provide valuable insights into minimal residual disease, tumor development and disease identification in relapse.

While genomic characterization of the medulloblastoma promises a more accurate molecular diagnosis, access to tumor tissue is complex due to its location and may require high-risk surgery and stereotactic biopsies, neither of which can guarantee access to a truly representative part of the tumor. Classification of this tumor type is also particularly difficult because of its constantly changing heterogeneity within the tumor, which requires in-depth and serial analysis of the developing genomic landscapes in response to treatment or during disease recurrence. Establishing the molecular composition of the medulloblastoma is particularly critical as this type of tumor is the most common of all pediatric brain tumors.

“The results of this present study represent a potentially practice-changing approach to fine-tune the surgical and clinical management of these young patients. By demonstrating the promise of cerebrospinal fluid as a liquid biopsy for the personalized treatment of this extremely aggressive disease, our results could spur us on Ultimately, they will develop more effective and tailored therapeutic strategies. Equally important, they can also reduce over-treatment to prevent long-term side effects, “notes author Joan Seoane, who also leads VHIO’s gene expression and cancer group.

“Medulloblastoma is a highly complex, heterogeneous type of tumor that develops over time. Currently, obtaining additional samples to monitor and track changes in the tumor to determine the most effective therapy in real time is a major challenge. Liquid biopsy of Liquor cerebrospinalis We want to respond to the critical need to refine the molecular characterization and monitoring of this disease, “adds Laura Escudero, lead author of the study and postdoc in Joan’s group at VHIO.

Hydrocephalus is an abnormal collection of cerebrospinal fluid and is very common in pediatric patients whose tumors grow in the posterior fossa area, including the medulloblastoma. In these cases, the cerebrospinal fluid must be drained prior to the operation to reduce the increased intracranial pressure (ICP). As the fluid is routinely collected for cytological evaluation, this facilitates easy access to samples for research in the laboratory.

This latest research – supported by funds from the Spanish Association Against Cancer (AECC) and the Fero Foundation – shows that cerebrospinal fluid assessment not only identify genomic changes during tumor progression even before surgery, but also detect disease recurrence and cancer can track progress to better inform real-time treatment decision-making. Data from the fluid biopsy are therefore of fundamental importance for the disease prognosis as well as for the measurement of tumor aggressiveness. This information is critical to both the surgeon and the oncologist when evaluating the risks and benefits of any intervention and therapeutic strategy.

The study’s researchers also show that CSF-ctDNA facilitates the subgrouping and risk stratification of patients with medulloblastoma, providing valuable insights for the diagnosis and prognosis of disease, in order to more effectively tailor therapies to the unique specificities of each individual patient. In particular, certain genetic mutations are critical when choosing treatment, such as mutations in the PTCH1 gene, which codes for a protein called patched-1. In this case, inhibitors of the Hedgehog signaling pathway may be a more effective treatment option.

“Our research represents an important step forward in better characterizing medulloblastoma, providing an earlier and more accurate molecular diagnosis, more closely monitoring our patients, and providing critical data on minimal development of residual disease and relapse. Larger cohort studies are now warranted . ” Bring cerebrospinal fluid closer to the clinic as a liquid biopsy and keep the promise of precision medicine to treat this disease, “concludes Joan Seoane.

Highly effective strategy for detecting tumors in common childhood brain tumors

More information:
Nature communication (2020). DOI: 10.1038 / s41467-020-19175-0 Provided by the Vall d’Hebron Institute for Oncology

Quote: Cerebrospinal fluid as a liquid biopsy for characterization and monitoring of medulloblastomas (2020, October 27), accessed on October 27, 2020 from https://medicalxpress.com/news/2020-10-cerebrospinal-fluid-liquid-biopsy-characterizing. html

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