Cerebrospinal fluid may be able to identify aggressive brain tumors in children

Date:
March 2, 2022
Source:
Johns Hopkins Medicine
Summary:
It may be possible to identify the presence of an aggressive
brain tumor in children by studying their cerebrospinal fluid,
according to new research.



FULL STORY ==========================================================================
It may be possible to identify the presence of an aggressive brain
tumor in children by studying their cerebrospinal fluid, according to
new research led by Johns Hopkins Kimmel Cancer Center investigators.


========================================================================== Comparing cerebrospinal fluid samples from 40 patients with
medulloblastoma - - the most common malignant brain tumor in children, accounting for 10% to 15% of pediatric central nervous system tumors --
and from 11 healthy children without the disease, investigators identified
110 genes, 10 types of RNA -- the machinery that translates proteins
-- called circular RNAs, 14 lipids and several metabolites that were
expressed differently between the two groups.

While these details were not specific enough to distinguish among the
four subtypes of medulloblastoma, they could be used to identify the
presence of cancer versus normal fluid.

A description of the work was published Feb. 24 in the journal Acta Neuropathologica Communications.

"We believe this is the first comprehensive, integrated molecular
analysis of the cerebrospinal fluid in medulloblastoma patients,"
says senior study author Ranjan Perera, Ph.D., director of the Center
for RNA Biology at Johns Hopkins All Children's Hospital (JHACH) in
St. Petersburg, Florida. Perera is also a senior scientist at the JHACH
Cancer & Blood Disorders Institute and an associate professor of oncology
at the Johns Hopkins University School of Medicine. He has a secondary affiliation with the JHACH Institute for Fundamental Biomedical Research.

"Our study provides proof of principle that all three molecular approaches
- - studying RNA, lipids and metabolites -- can be successfully applied
to cerebrospinal fluid samples, not only to differentiate medulloblastoma patients from those without the disease, but also to provide new insights
into the pathobiology of the disease," Perera adds.

"This study provides data for novel biomarkers to detect and track medulloblastoma, which are very much needed to enable improved patient outcomes," says Chetan Bettegowda, M.D., Ph.D., Jennison and Novak
Families Professor of Neurosurgery at Johns Hopkins. "This work
also forms the theoretical basis for examining similar biomarkers
for other types of brain cancers and other neurological disorders."
Current diagnosis is based on clinical assessment, imaging and biopsies
from tumor tissue. There is an unmet need for diagnostic tests to detect
the disease sensitively during the initial presentation and especially
during any recurrences, because recurrences are not always seen on
magnetic resonance imaging (MRI), Perera says.

Liquid biopsy -- the molecular analysis of biofluids -- is a minimally
invasive method that shows promise for disease detection and monitoring
by measuring circulating tumor cells, DNA, RNA or other substances in the urine, cerebrospinal fluid and blood samples. Because cerebrospinal fluid bathes the brain and spinal cord, it was considered a way to provide a
window to tumors arising in the central nervous system and disseminating
in the fluid, Perera says.

During the study, Perera and colleagues used gene sequencing, metabolic
and lipid profiling laboratory techniques to tease out the differences
in RNA, metabolites and lipids in cerebrospinal fluid samples from
patients with medulloblastoma and healthy controls. Patients with medulloblastoma were found to have a unique RNA metabolic and lipid
landscape in their fluid that might be helpful for diagnosis and
monitoring, and that reflects biological changes consistent with the
presence of medulloblastoma in the central nervous system, Perera
says. The metabolite and lipid profiles both contained indicators of
tumor hypoxia -- a condition in which tumor cells were deprived of oxygen.

More studies in larger patient populations are necessary to confirm the findings, Perera says. The analysis provides several biomarkers that
can be studied further.

The work was supported in part by the Schamroth Project funded by Ian's
Friends Foundation, the Hough Family Foundation, Susan and Robb Hough,
and the National Cancer Institute (grant 1R37CA230400).

In addition to Perera and Bettegowda, study co-authors were Bongyong Lee, Rudramani Pokhrel, Menglang Yuan, Stacie Stapleton, George Jallo and
Charles Eberhart of Johns Hopkins; Iqbal Mohamad and Timothy Garrett of
the University of Florida College of Medicine in Gainesville and Rabi
Murad of the Sanford Burnham Prebys Medical Discovery Institute in La
Jolla, California.

special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by Johns_Hopkins_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Bongyong Lee, Iqbal Mohamad, Rudramani Pokhrel, Rabi Murad, Menglang
Yuan, Stacie Stapleton, Chetan Bettegowda, George Jallo, Charles G.

Eberhart, Timothy Garrett, Ranjan J. Perera. Medulloblastoma
cerebrospinal fluid reveals metabolites and lipids indicative
of hypoxia and cancer-specific RNAs. Acta Neuropathologica
Communications, 2022; 10 (1) DOI: 10.1186/s40478-022-01326-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220302125105.htm

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