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Better diagnosis for children with brain tumors through epigenetic profiling

9 November, 2022

NEW STUDY. An in-depth genetic analysis of tumor samples from all children with brain and spinal cord tumors may provide a more accurate diagnosis. In a new study, researchers at the University of Gothenburg show that analyses of the methylation profile of tumors can be used. This analytic method has already been introduced at Sahlgrenska University Hospital.

Tumors of the brain or spinal cord are rare in children, accounting for about 80 new cases in Sweden each year. A wide range of tumor types can be involved, and it is sometimes challenging for healthcare providers to make the right diagnosis. Depending on the location and type of tumor, they cause different symptoms, have different prognoses, and require different treatments.

Regulates how genes are used

Cancer is usually caused by genetic changes (mutations) in the DNA of cells. These changes may be congenital, but they can also occur spontaneously during a lifetime.

In addition to mutations in DNA, cancer can also be caused by epigenetic changes. Epigenetics is the machinery in cells that regulates how genes are used and controls how a cell develops. It has been demonstrated that the epigenetic process influences the development of cancer and plays an important role in the diagnosis of brain tumors.

In a national study, tumor material has been collected from all children operated on in Sweden for brain and spinal cord tumors 2017–2020. Samples were taken from 240 children. These samples were analyzed in Gothenburg and classified using an algorithm based on information from thousands of brain tumors.

Unique profile

Helena Carén. Photo: Malva Carén.

“We have focused on the part of epigenetics called DNA methylation, which regulates gene expression. We developed a unique profile for each tumor by measuring where the methyl groups are located on the DNA strand in the tumor sample,” says Helena Carén, associate professor and cancer researcher at Sahlgrenska Academy at the University of Gothenburg, who headed the study.

The results show that classification based on the methylation profile correlated closely with standard diagnosis of the children. For 78 per cent of the samples, the DNA methylation profile could be linked to a specific tumor class. In most cases, this was consistent with the established diagnosis. However, 14 of the children (six percent of the samples) received a different diagnosis, and for 11 of these children (five percent of the samples), the new diagnosis would have affected the clinical treatment that the children received.

A more precise diagnosis

Elizabeth Schepke. Private photo.

“We can conclude that methylation analysis provides a more precise diagnosis, and in five percent of these cases, the result of this analysis would have a direct impact on clinical treatment. The study shows that the DNA methylation profiles can be used as an integrated tool in clinical diagnostics,” says Elizabeth Schepke, the study’s lead author. She is a doctoral student at Sahlgrenska Academy at the University of Gothenburg and pediatric oncologist at the Childhood Cancer Center at Sahlgrenska University Hospital.

The findings have been published in the journal Neuropathology and Applied Neurobiology. Regional childhood cancer centers throughout Sweden and Sahlgrenska University Hospital collaborated on the study.

Maja Löfgren. Private photo.

“The analysis worked well on all types of tumors, even those with a relatively low tumor cell count, which is important information for clinical work,” says Maja Löfgren, a co-author of the study and researcher at Sahlgrenska Academy at the University of Gothenburg.

Steps toward precision medicine

More and more children and young people now survive cancer. Usually, the tumor is removed by surgery, followed by treatment, such as cytostatic drugs, another operation, radiation, and possibly targeted therapy. However, many of the children live for a long time with side effects and complications after the disease and treatment.

The study represents a clear step toward precision medicine for brain tumors in children. The results have already led to DNA methylation being mapped for all brain and spinal cord tumors removed from children in Sweden. The analyses are carried out at Sahlgrenska University Hospital, where the method is also used for samples from some adult patients.

For cases that appear more complicated, the method of analyzing the epigenetic pattern in children with brain tumors is also used internationally at some hospitals. This study demonstrates that the method can also be useful for diagnoses that appear less complicated.

Title: DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study; https://doi.org/10.1111/nan.12838

BY: ELIN LINDSTRÖM

By: Elin Lindström
Tagged With: Cancerforskning, institutionen för biomedicin, Ny studie, Sahlgrenska Universitetssjukhuset, vetenskaplig publicering

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Information from Sahlgrenska Academy Research Support Office

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