Structured DNA from genes that code the “leukemic cell” – resulting in a patient with a high-risk of developing the disease – is significantly different from those codenomics that code the DNA in the corresponding organ. This fact, in a retrospective study from eight African American patients, Michigan Medicine scientists have found may provide insight into why these two groups of patients are biologically at high risk for pancreatic cancer.
“We are very pleased that we identified an association between structural DNA methylation and pancreatic cancer with higher risk of the disease, ” said Dr. Agne Velthut-Meafsson, director of the Karolinska Institute’s Lung Cancer Research Program, and an associate professor at the Department of Medicine in Huddinge, Sweden. “Identified differences highlight an outside chance of causal modification of DNA, and if known, could lead to new therapeutic options. “
The team’s results are published in Cell Reports.
“To bring our results to the clinic, we followed patients for nine years of follow-up, including one successful ledipasato – a pancreatic cancer originated in Africa, ” said Dr. Josef Bute-Bison, a researcher at the Swedish Cancer Society and one of the lead authors of the study.
“We quantified viral DNA methylation, which reflects methylation of the viral genome, ” said Lead author Dr. Sigrid Kornblom, a professor of medicine at the University of California-San Francisco. “Overall, the DNA methylome is different between the leukemic cell and the leukocytes, and the leukemic cell has gene regulators that interact with gene promoters. “
Using this approach, the investigators were able to reproduce those deleted genes found in the leukemic cell, as well as to look for DNA methylome-resident genes in the leukocytes. The researchers were therefore able to reveal DNA methylome-resident genes that clearly differed between cancer and healthy human patients.
“Our study reveals that altered DNA methylome-resident genes in cancer cells are more related to the leukemic cell than the tumor, ” said Velthut-Meafsson. “Maybe, the leukemia cell can suppress tumor methylation, randomizing which genes may become active and which genes will be silenced. We investigated this through different methods and different mutations in the leukemic cell. We found a chromosomal structural variant, which allows us to understand which genes are regulated by chromosomal structural modifications. “