Cardia cancer in Chinese patients could be due to local dietary habits
In an area in northern China, cancer in the cardia occurs at high rates and the cancer type has distinct features compared to Western countries. Together with Chinese colleagues, Xingqi Chen’s research group at IGP have found that the presence of many copies of the ERBB2 gene can be correlated with better prognosis for patients with cardia cancer. The genetic alterations could be due to local dietary habits in the area.
Cancer is generally associated with a range of genetic alterations, for instance the presence of DNA outside the chromosomes. This extrachromosomal DNA can contain genes that have been amplified into several copies by focal amplification of DNA regions. In a study published in the journal Nature Communications, the researchers have found that extrachromosomal DNA and focal amplifications were common in a group of Chinese patients with cancer in the cardia, which is located between the esophagus and the stomach.
“We studied samples from patients in the Taihang Mountains of north central China, where there is a high incidence of cardia cancer. We think that the extrachromosomal DNA and focal amplifications that we detected could be due to a high degree of DNA damage caused by the substance nitrosamine in the local diet,” says Xingqi Chen, who has led the Swedish part of the study.
When the researchers examined the genes in the amplified DNA, they found a correlation between specific genes and the patients’ prognosis. Focal amplification of the gene EGFR was correlated with worse prognosis while focal amplification of the ERBB2 gene was linked to a better prognosis. When they studied the correlation between the protein encoded by the ERBB2 gene and prognosis they found that survival probability depended on the protein level of ERBB2.
“If the surviving time was less than two years, patients with ERBB2 had a lower survival probability than patients without ERBB2. However, when their surviving time was longer than two years the tendency was the opposite, that is, patients with the ERBB2 protein had a higher survival probability. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in cardia cancer patients with longer surviving time,” says Xingqi Chen.
Rare genetic variants are not the main cause of common diseases
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
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
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
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
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
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
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
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.