DNA breaks early in replication process associated with B cell cancers

  • Posted: January 24, 2013
NCI Press Office


Research by scientists at the NCI has identified a new class of DNA sites in cells that break early in the replication process. They found that these break sites correlate with damage often seen in B cell cancers, such as diffuse large B cell lymphoma. All cells undergo DNA replication, a process where the cell copies its entire genome before cell division. Some genes that comprise DNA strands increase the risk for cancer, induce replication stress, and result in a higher likelihood of cells acquiring DNA damage, such as breaks. Replication stress may be one of the earliest events leading to genome instability that can cause cancer. This study is the first to describe an underlying mechanism of genome instability in B cell cancers that could not previously be explained. This research was headed by Andre Nussenzweig, Ph.D., chief of the Laboratory of Genome Integrity, Center for Cancer Research, NCI.  Results of this finding appeared in Cell, Jan. 31, 2013.

Nussenzweig and collaborators wanted to find if there were specific places within a cell’s DNA that were more difficult to copy and, as a result, caused DNA breaks. They used the mouse immune system as a model, isolated healthy cells, and then monitored the cells for initiation of DNA damage in order to understand how a healthy cell mutated. Proteins that repair the damage by binding to the affected DNA sites were mapped, using genome-wide sequencing techniques. The scientists then compared the DNA damage sites in their mouse model with sites mutated in human diffuse large B cell lymphoma tissue samples, providing important evidence that both mouse and human cells exhibit similar trends of genome instability. As a result, their findings in mice may be important in B cell lymphoma initiation and progression in humans. As a next step, the investigators will begin mapping the DNA damage induced by replication in other cell types to learn if they too are involved in cancer progression.