Research provides new insights into the prevention and treatment of brain tumors in children

a child at St. Jude Children's Research Hospital in the United States, who had a very rare form of leukemia, and whose father died of brain cancer two or three years ago at the age of 31.
time, researchers found that a defective gene, P53, was passed down from generation to generation, a carcinogen. "Is this the cause of cancer in boys?" It feels like this... But we're not sure. "Perhaps the questions that plagued pediatric oncologist Michael Walsh at the time were about to be answered.
an unprecedented "protein genomics" study that analyzed proteins, genes, and RNA transcriptions involved in pediatric brain tumors to provide a more comprehensive understanding of such tumors. The results could help doctors more accurately identify different types of tumors and treatments. On November 26th, the paper was published in Cells.proteomics is a research area that junctions proteomics with genomics. Although the genome is the blueprint for proteins, these proteins are the main force of every living cell in the body. In order to understand the genome, people need to have a good understanding of proteomics, including their post-translation modification (PTM).
although single-cell RNA has been widely used in cancer research, deep proteomic analysis is not yet able at the single-cell level. Therefore, mass spectrometrometography based on larger tissues is now an important means of large-scale proteomics and PPM identification.
, pediatric brain tumors are the second-largest cause of cancer death in children, after leukemia. Some pediatric brain tumor types have poor prognosis, with a five-year survival rate of less than 20%, such as high-level gliomas and atypical teratoma-like transverse muscle tumors. Improving treatment strategies for children is urgent.
Wang Pei, lead author of the study and a professor of genetics and genomics at mount Sinai's Icahn School of Medicine, said in an interview with the China Science Journal that precise drug methods are needed to limit the toxicity that harms brain development when treating pediatric brain tumors. "Despite the great efforts of precision medicine based on genomics over the past decade, targeted treatment of pediatric brain tumors based on genomic information has been largely unsuccessful." "So we want to go deep into the protein 'world' and have a new understanding of these tumors, which was a missing link until this study," she said. In
, pediatric cancers, especially pediatric brain tumors, have relatively low mutations. "Therefore, a comprehensive description of the molecular biology of these tumor functions, including protein genomic analysis, is essential for better understanding and treatment of pediatric brain tumors.Based on this, researchers from organizations such as the American Alliance for Clinical Proteomic Oncology Analysis (CPTAC), the Children's Brain Tumor Network (CBTN), the Icahn School of Medicine at Mount Sinai, the National Cancer Institute, the Fred Hutchinson Cancer Research Center, the National Children's Hospital and the Children's Hospital of Philadelphia collected and analyzed genetic, genomic and proteomic data on multiple types of brain tumors in children. The study is the first comprehensive study of the childhood brain cancer genome (designed to describe DNA sequence changes in samples), transcription groups (copies of quantified RNA), holistic proteomics (identification and quantification of proteins), and phosphate proteomics (quantitative active proteins). The researchers analyzed 218 tumor samples involving seven different types of brain tumors.
study involved hundreds of researchers from nearly 40 different research institutions. Its success is the result of the joint efforts of researchers, doctors, patients, family members, etc. Wang Pei said.
" joint study is a commitment to data sharing and open science. Our collaboration provides an opportunity for CPTAC and CBTN to expand the resources available to us and answer extremely important biological questions. Using the collective wisdom of these professional organizations, we are able to better understand the mechanisms of pediatric tumors, improve the identification process of target proteins, and potentially improve cancer treatment. Adam Resnick of Children's Hospital of Philadelphia, co-chair of CBTN Academics, who was involved in the study, said.
also noted that due to the complexity of the project, data generation involves coordination among many research laboratories. Quality control after data generation is also an important component. CPTAC has established a very rigorous program to perform multi-layered protein genomic data quality checks and pre-processing.by describing the biological themes common to these different types of tumors, the researchers offered new insights, pointing out that current treatments for specific types of tumors can be used on other tumors with the same proteomic characteristics.
specifically, the researchers uncovered two different sub-groups of children with cranial pharyngophal tumors, a pediatric brain tumor. The proteomics/phosphate proteomics characteristics of one subgroup are strikingly similar to the other type of tumor, a low-grade glioma with a BRAFV600E mutation. This observation suggests that MEK/MAPK inhibitors, a chemotherapy drug already used to treat these gliomas, may also be useful in treating craniofacial tube tumors, which currently do not have a strong chemotherapy option.
said they had submitted a clinical trial proposal for cranial pharyngoma in collaboration with the Pacific Society of Pediatric Neurocology (PNOC). These trials are expected to start soon to test the effectiveness of inhibitors in some children with cranial pharyngoma.
team also used a wealth of clinical results data to identify new prognostic biomarkers for a tumor called high-level glioma (HGG). When HGG has a gene mutation called H3K27M, they tend to be highly aggressive and patients live relatively short. The researchers found that the richness of IDH1 and IDH2 proteins in tumor tissue could help identify genes with un mutated H3K27M that are also less invasive.
" combination of clinical, proteomic and genetic data from this study allows us to build a more comprehensive biological model of brain tumors for more targeted treatment. Brian Rood, director of the Brain Tumor Institute at the National Children's Hospital, told reporters.
are conducting large-scale protein genome studies of adult glioblastomas and young glioblastomas. Understanding these brain tumors in the context of brain development and determining treatment options for different age groups will be important.
"We have revealed for the first time the power of proteins in pediatric brain tumors to better determine which patients might benefit from a given treatment." Amanda Paulovich, one of the authors of the paper and a professor at the Fred Hutchinson Cancer Research Center, said, "As this work moves further into clinical life, I hope it will bring comfort to patients with this terrible disease and their families." (Source: Tang Feng, China Science Journal)
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