NIH scientists reveal origin of cancer-causing translocations


Scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have published a new study in the journal Nature that answers one of cancer's biggest questions: how translocations (or recurrent chromosomal rearrangements) lead to the development of lymphoid cancers (lymphoma and leukemia) in humans.

Science has known that translocations can cause cancer since 1960. They happen when broken strands of DNA from a chromosome are joined together with a different chromosome, deregulating genetic information and causing cellular transformation. While this isn't always a bad thing, it is when a cancer develops.

Many theories have been put forth as to origin of the rearrangements that turn malignant. In this new study by the NIAMS, they put many of the best ones to the test.

Using B-cells, they discovered that "the frequency of DNA damage was directly proportional to the frequency of translocation." Further, an enzyme called AID can damage about 150 genes within the genome of a B-cell, making them vulnerable to translocations. Many of those 150 genes have been identified previously as being translocations that occur in cancers.

In the absence of AID, translocations were driven chiefly by how frequently gene proximity or interaction frequency.

The end result is a potential new pathway to reduce cancer risk or in some cases prevent it may lie in finding ways to stop the damage done by AID.

Source: US National Institutes of Health

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