Scientists resolve how chromosomal mix-ups lead to tumors

March 29, 2012 in Cancer

(Medical Xpress) -- A new study by scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health, resolves longstanding questions about the origin of recurrent chromosomal rearrangements — known as translocations — that drive lymphomas and leukemias in humans. Translocations occur when broken strands of DNA from one chromosome are erroneously joined with those of another chromosome, thus deregulating genetic information and leading to cell transformation. Sometimes chromosomal rearrangements can be beneficial, in that they enable the immune system to respond to a vast number of microorganisms and viruses. However, translocations can result in tumors. The study was reported in the journal Nature.

Specific chromosomal translocations driving human have been known since 1960, when scientists in Philadelphia (Peter Nowell and David Hungerford) first visualized one such lesion in patients suffering from chronic myeloid leukemia, an aggressive form of cancer in the blood. The origin of such malignant rearrangements, however, has been unclear. At least three theories have been put forward to explain their etiology: 

  • Translocations between two  are driven primarily by how frequently the genes interact in the nucleus of tumor precursor cells.
  •  
  • Translocating genes undergo DNA damage more frequently than non-translocating genes.
  •  
  • All genes in the genome have about an equal chance of translocating with one another, but certain translocations are particularly selected because they drive cell transformation.
 In the new study, NIAMS scientists used cutting-edge technologies to explore the three theories.  Using immune cells known as B cells, they found that the frequency of DNA damage was directly proportional to the frequency of translocation. Intriguingly, the researchers found that an enzyme, called AID, damages approximately 150 genes in the B cell genome, thus making them susceptible to translocations. Among the targeted genes, many have been previously shown to be translocated in human cancer. Further study also revealed that, in the absence of AID, gene proximity or interaction frequency was the driving force behind translocations.

The new results not only clarify the origin of tumor-inducing translocations, but they also suggest that finding ways to stop AID could potentially prevent the development of many human cancers.

More information: Ofir Hakim et al. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature DOI: 10.1038/nature10909 [Epub ahead of print]

Journal reference: Nature search and more info website

Provided by National Institutes of Health

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

New fluorescent tools for cancer diagnosis

In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...

Cancer created 2 hours ago | popularity not rated yet | comments 0

Modulating the immune system to combat metastatic cancer

Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...

Cancer created 2 hours ago | popularity not rated yet | comments 0

Scientists put bowel cancer under the microscope

Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.

Cancer created 5 hours ago | popularity 5 / 5 (1) | comments 0

Researcher identifies breast cancer fighting hormone

Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.

Cancer created 6 hours ago | popularity 5 / 5 (1) | comments 0

Ground breaking cancer research finds immune system link

(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.

Cancer created 6 hours ago | popularity 5 / 5 (3) | comments 0


Researchers identify first drug targets in childhood genetic tumor disorder

Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...

Pollen count apps for smartphones are nothing to sneeze at

Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.

FDA warns of infections tied to Tennessee pharmacy

(AP)—Government health officials are investigating several health problems reported with potentially contaminated medications made by a Tennessee specialty pharmacy.

Engineered cytomegalovirus protects monkeys from HIV equivalent

(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...

Hormone levels may provide key to understanding psychological disorders in women

Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.

Going live: Immune cell activation in multiple sclerosis

Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...