Study shows how cancer remodels human chromosomes for its own purposes

Scientists from the University of Virginia have shown that cancer rebuilds the architecture of human chromosomes, which allows the disease to take hold and spread.

Study shows how cancer remodels human chromosomes for its own purposes
Chongzhi Zang, Ph.D., has shed light on how cancer remodels our chromosomes for its own purposes. Image Credit: University of Virginia Health System.

A remodeling like this is significant because, within the human chromosomes, the organization of the components actually impacts the functions of human genes. With such renovations, cancer starts to make a comfortable abode for itself within the human cells.

Even when the genetic code in DNA sequence may largely remain the same, the three-dimensional structure of chromosomes in cancer can be very different from our normal cells. A better understanding of the cancer genome structure can give us insights for developing new drugs to specifically target the Achilles’ heel of each cancer.”

Chongzhi Zang, PhD, Researcher and Computational Biologist, Center for Public Health Genomics, University of Virginia

Understanding cancer

Cancer depends on a protein, known as the “CCCTC-binding factor” (CTCF), to make its preferred changes within the human chromosomes. CTCF appears naturally in human cells. It plays a crucial role in healthy cells by maintaining the structure of chromosomes and switching genes on and off as required.

However, Zang found that CTCF is seized by cancer for its own purposes. The CTCF does not attach where it should and occurs where it should not. This changes the 3D organization of human chromosomes and alters the pattern of gene function.

To interpret the role of CTCF in cancer, Zang and his group comprehensively studied the genomic information obtained from human cancer and tissue samples.

The team detected patterns of CTCF remodeling in six types of cancers, such as acute myeloid leukemia, T-cell acute lymphoblastic leukemia, colorectal cancer, breast cancer, prostate cancer, and lung cancer.

We developed an innovative data science approach to collect and integrate thousands of publicly available datasets to make these findings. It’s exciting to see how many new scientific discoveries can be made solely by analyzing the big data that’s already out there.”

Chongzhi Zang, PhD, Researcher and Computational Biologist, Center for Public Health Genomics, University of Virginia

The investigators verified their finding s by specifically examining the T-cell acute lymphoblastic leukemia, but according to them, additional studies into the CTCF binding changes will also allow researchers to better interpret the origins of other types of cancers.

(Moreover, faulty CTCF binding has been associated with various conditions, including developmental disorders, and hence a better understanding of this defective binding may also provide crucial insights into those disorders.)

The abnormal patterns of CTCF binding that we found is probably a signature existing in every cancer type. These findings brought us one small step closer to fully unraveling the molecular mechanism of cancer, an extremely complex disease.”

Chongzhi Zang, PhD, Researcher and Computational Biologist, Center for Public Health Genomics, University of Virginia

Source:
Journal reference:

Fang, C., et al. (2020) Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation. Genome Biology. doi.org/10.1186/s13059-020-02152-7.

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