Researchers identify potential biomarker to distinguish two aggressive types of pediatric brain tumors – ScienceDaily

It may soon be possible to identify Group 4 medulloblastomas – the most common malignant brain tumors in children – from the most aggressive Group 3 medulloblastomas. According to researchers at the Johns Hopkins Kimmel Cancer Center, research that relies on a little-explored part of the RNA, which produces proteins, could lead to the development of better targeted cancer treatments.

Four groups of medulloblastomas have been identified, with group 3 being the most aggressive—the 5-year survival rate is 45% to 60%. Group 4 is the most common form of medulloblastoma, accounting for 35-40% of all cases.

The results were published on August 22 in the journal advances in neuro-oncology.

So far, it is difficult to distinguish Group 3 tumors – which have a better prognosis (five-year survival 75%-80%) – from Group 4 tumors. Group 3 treatment is more aggressive than Group 4, and often includes radiotherapy. . Differentiating between group 3 and group 4 medulloblastomas is based on immunohistochemistry of tissue samples—specialized tests used to distinguish types—and imaging.

Said study senior author Ranjan Pereira, Ph.D., director of the Center for RNA Biology at Johns Hopkins Hospital for All Children (JHACH) in St. Petersburg, Florida. Pereira is also a senior scientist at the JHACH Institute of Cancer and Blood Disorders and an associate professor of oncology at the Johns Hopkins University School of Medicine. He has a secondary affiliation with the JHACH Institute for Basic Biomedical Research.

In particular, the researchers looked at long noncoding RNA (lncRNA), which experts believed did not play a role in building proteins. However, new evidence has found that it plays a role in regulating gene expression that influences cancer growth and behavior.

Pereira and the investigators found that a lncRNA gene called lightis highly expressed in group 4 medulloblastomas, but not group 3. “We found that this long non-coding RNA (light) interacts with a single gene called SMYD3,” He said. SMYD3 It regulates the endothelial growth factor receptor (EGFR), which helps cancer develop new blood vessels that feed the tumor.

“clearly, light It could act as a biomarker for group 4 because we haven’t seen that in group 3 or the other two groups,” he says.

Researchers studied light in mice and human models of medulloblastoma and observed that developing tumors were smaller than cells without them light. Tumor growth was also slower in models where light brokenAnd the role support light in tumor growth and spread.

The investigators also conducted laboratory analyzes that showed this light It interacts with another protein called PTPB1, which regulates SMYD3 protein production. This pathway enhances the expression of EGFR in group 4 medulloblastomas – potentially providing a target for therapy. There are several drugs out there that inhibit EGFR. Of course, much work is needed to understand the molecular mechanisms of light A course in group 4 medulloblastomas prior to investigation of therapies.

In addition to Pereira, study co-authors were Bong Yong Lee, Keisuke Katsushima, Rudramani Bookrell, Minglang Yuan, Stacey Stapleton, George Gallo and Charles Eberhart of Johns Hopkins. Robert J. Wechsler-Ria of the Sanford Burnham Priebus Institute for Medical Discovery in La Jolla, California; and Animesh Ray from the Keck Graduate Institute in Claremont, California, and the California Institute of Technology in Pasadena, California.

The work was supported in part by the Schamroth Project funded by Ian’s Friends, the Hough Family Foundation, Susan and Rob Hogg to Ranjan J. Pereira and George Gallo, and an NCI grant to Ranjan J. Pereira and Charles Eberhart (1R37CA230400).

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