A recent study published in the journal Nature by scientists at UT Southwestern Medical Center has shed light on a new class of chromosomal abnormalities that may be responsible for cancers and congenital disorders. Despite the fact that dividing cells aim to accurately segregate their genome into two genetically identical daughter cells, this process can often go wrong, leading to the rapid evolution of genomic changes that fuel cancer proliferation.
The paper focuses on chromothripsis, a term derived from Greek that describes the catastrophic shattering of chromosomes into small fragments. The researchers investigated how shattered chromosomes from abnormal structures called micronuclei move during cell division and found that the chromosome fragments remained stuck together, allowing the shattered chromosome to segregate as a unit into one of the two daughter cells. However, the cell’s DNA repair machinery haphazardly stitched the pieces back together in the incorrect order to form a rearranged chromosome.
The researchers identified a protein complex consisting of CIP2A and TOPBP1 that tethers the DNA fragments together during cell division. This process results in the loss of critical tumor suppressor genes and can be detected across 25 cancer types. The findings build on previous work by Dr. Peter Ly, who has engineered unique experimental systems to re-create and study chromothripsis in the laboratory.
Dr. Ly, a member of the Harold C. Simmons Comprehensive Cancer Center and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, said that “these findings provide a fundamental understanding of how diverse patterns of chromosomal alterations form and drive cancer development.” His lab plans to continue studying the role of CIP2A-TOPBP1 in maintaining genome stability and whether this protein complex could be a relevant target for cancer treatment.
Source: UT Southwestern Medical Center