Subgroups of brain tumours associated with cell origin and disease prognosis
2022-04-25
Researchers at IGP have detected different subgroups of the brain tumour form glioblastoma, where the cancer cells’ properties depend on which cell type they originate from. The used analysis method could also separate glioblastoma patients with significant differences in survival. The findings open up for identifying specific therapeutic targets for the new subgroups of glioblastoma.
Glioblastoma is the most frequent and most lethal primary malignant brain tumour, with more than 300 cases per year in Sweden. Despite intensive therapy with surgical resection, radiotherapy and chemotherapy, most patients die within one year after diagnosis due to disease relapse. There is a lot of information available about the genetics behind glioblastoma but this has so far not resulted in any therapeutic breakthroughs and only a few markers for disease prognosis.
In a study published in the journal Nature Communications, three research teams have worked in close collaboration and analysed glioblastoma cells from 58 patients. They used a sequencing technology that generates global information about of the cancer cells’ epigenetics, i.e. changes in the genome that are not caused by direct mutations.
“The work is based on our previous studies where we show that different glioblastoma progenitor cells have a great impact on tumour development and important properties of the cancer cells. Since epigenetic analysis is a very sensitive method for distinguishing normal cell types, we hoped that it would also provide new knowledge about developmental biological mechanisms in glioblastoma,” says Lene Uhrbom, who led the study together with Xinqi Chen.
The researchers used the unique, local biobank HGCC (Human Glioblastoma Cell Culture), which consists of glioblastoma cells from patients, and analysed samples from the biobank with a new sequencing technology called ATAC-seq. By separating the patients based on the epigenetic information of their glioblastoma cells, they were able to identify three groups in which also central functional properties of the cancer cells, such as cell division, invasiveness and treatment resistance, were found to be distinct.
Two of the groups also showed a significant difference in patient survival. This has not been shown in previous molecular analyses because the two groups are very similar and have belonged to the same genetic subgroup.
“To understand the background for the epigenetic groups of glioblastoma, we compared the patient data with the same type of epigenetic analysis of glioblastoma cells from mouse models, where the tumours originated from three different normal cell types in the brain. We found a link between the different cells of origin in mice and the three patient groups of glioblastoma. This strengthens the relationship between developmental biological origin and the properties of tumour cells, says Xingqi Chen.
The findings may lead to refined prognostic tools and open up for the development of targeted therapy for defined subgroups of glioblastoma patients.
More information:
Article in Nature Communications
Xingqi Chen’s research
Lene Uhrbom’s research
-
Rare genetic variants are not the main cause of common diseases
2022-05-13
Although some rare variants can significantly increase the risk of disease for a few individuals, the majority of the genetic contribution to common diseases is due to a combination of many common genetic variants with small effects. This is shown by researchers at IGP and other departments at Uppsala University in a new comprehensive study published in the journal Nature Communications.
-
Subgroups of brain tumours associated with cell origin and disease prognosis
2022-04-25
Researchers at IGP have detected different subgroups of the brain tumour form glioblastoma, where the cancer cells’ properties depend on which cell type they originate from. The used analysis method could also separate glioblastoma patients with significant differences in survival. The findings open up for identifying specific therapeutic targets for the new subgroups of glioblastoma.
-
Armed CAR-T cells to better fight cancer
2022-04-04
Immunotherapy is increasingly becoming a successful way to treat cancer. Researchers at IGP have now developed armed CAR-T cells that reinforce the immune defence against cancer and that could increase the possibilities to successfully treat solid tumours. The study has been published in the journal Nature BioMedical Engineering.
-
Inflammation and net-like protein structures in cerebral cavernous malformations
2022-03-28
In the condition known as cavernoma, lesions arise in a cluster of blood vessels in the brain, spinal cord or retina. Researchers at IGP now show in a new study that white blood cells and protein structures associated with the immune response infiltrate the vessel lesions. The findings support that inflammation has a role in the development of cavernoma and indicate a potential biomarker for the disease.
-
Protein landscape on cancer cells mapped with new technology
2022-03-03
In recent years, great advances have been made in the development of new, successful immunotherapies to treat cancer. Two types of targeted immunotherapies that have revolutionised areas of cancer care are CAR T-cell therapy and antibody treatments. However, there are still significant challenges in the identification of cancer cell surface proteins that function as targets for immunotherapies. Mattias Belting, professor at Lund University and senior consultant at Skåne University Hospital, and guest professor at IGP, is well on the way and his group’s findings are now published in the journal PNAS.
-
CRISPR-Cas9 can generate unexpected, heritable mutations
2022-02-03
CRISPR-Cas9, the “genetic scissors”, creates new potential for curing diseases; but treatments must be reliable. In a new study, researchers have discovered that the method can give rise to unforeseen changes in DNA that can be inherited by the next generation. These scientists therefore urge caution and meticulous validation before using CRISPR-Cas9 for medical purposes.
-
New technology to study DNA in archived tissue samples
2022-01-19
Researchers at IGP have developed a technology that allows studies of DNA profiles in archived tissue samples. The technology permits investigators to better understand regulation of gene activity in cancer and precision medicine.
-
New genes associated with relapse of acute myeloid leukemia
2022-01-13
In the blood cancer type acute myeloid leukemia, it is common that patients relapse some time after treatment. Researchers from IGP have in a new study identified genes that seem to be associated with the risk of relapse. The findings may form the basis for new treatment strategies and contribute to better survival for patients with acute myeloid leukemia.