Featured Research

from universities, journals, and other organizations

New technique identifies first events in tumor development

Date:
September 29, 2011
Source:
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Summary:
A novel technique that enables scientists to measure and document tumor-inducing changes in DNA is providing new insight into the earliest events involved in the formation of leukemias, lymphomas and sarcomas, and could potentially lead to the discovery of ways to stop those events.

A novel technique that enables scientists to measure and document tumor-inducing changes in DNA is providing new insight into the earliest events involved in the formation of leukemias, lymphomas and sarcomas, and could potentially lead to the discovery of ways to stop those events.

Related Articles


Developed by a team of researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Cancer Institute (NCI), both parts of the National Institutes of Health, and The Rockefeller University, the technology focuses on chromosomal rearrangements known as translocations. Translocations occur when a broken strand of DNA from one chromosome is erroneously joined with that of another chromosome. Sometimes these irregularities can be beneficial in that they enable the immune system to respond to a vast number of microorganisms and viruses. However, translocations can also result in tumors.

The findings are reported in the Sept. 30 issue of the journal Cell.

Translocations can take place during the course of normal cell division, when each chromosome -- a single strand of DNA containing many genes -- is copied verbatim to provide genetic information for the daughter cells. Sometimes, during this process, byproducts of normal metabolism or other factors can cause breaks in the DNA.

"The cell expresses specific enzymes whose primary purpose is to repair such lesions effectively, but when the enzymes mistakenly join pieces of two different chromosomes, the cell's genetic information is changed," said Rafael C. Casellas, Ph.D., senior investigator in the Genomics and Immunity Section at the NIAMS, who led the research team along with Michel C. Nussenzweig, M.D., Ph.D., from Rockefeller.

Casellas likens the phenomenon to breaking two sentences and then rejoining them incorrectly. For example, "The boy completed his homework." and "The dog went to the vet." might become "The dog completed his homework." or "The boy went to the vet." When a cell gets nonsensical information such as this, it can become deregulated and even malignant.

Scientists have known since the 1960s that recurrent translocations play a critical role in cancer. What was unclear was how these genetic abnormalities are created, since very few of them were studied, and only within the context of tumors, said Casellas. To better understand the nature of these tumor-inducing rearrangements, the authors had to create a system to visualize their appearance in normal, non-transformed cells.

The system the teams created involved introducing enzymes that recognize and cause damage at a particular sequence in the DNA into cells from mice, thereby constructing a genome where a unique site is broken continuously. The group then used a technique called polymerase chain reaction -- which allows scientists to quickly amplify short sequences of DNA -- to check all the sites in the genome that would get translocated to this particular break. Using this technique, they were able to examine more than 180,000 chromosomal rearrangements from 400 million white blood cells, called B cells.

Based on this large data set, the scientists were able to make several important observations about the translocation process. They learned that most of the translocations involve gene domains, rather than the space on the DNA between the genes. They also found that most translocations target active genes, with a clear bias for the beginning of the gene, as opposed to its middle or end. The team also showed that a particular enzyme that normally creates DNA breaks in B cells dramatically increases the incidence of translocations during the immune response. This feature explains the long-standing observation that more than 95 percent of human lymphomas and leukemias are of B cell origin.

"This knowledge is allowing us to understand how tumors are initiated," said Casellas. "It is the kind of information that in the near future, might help us prevent the development of cancer."

Additional support for this work was provided by Andre Nussenzweig, Ph.D., who heads the Laboratory of Genome Integrity of NCI.


Story Source:

The above story is based on materials provided by NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Note: Materials may be edited for content and length.


Journal Reference:

  1. Isaac A. Klein, Wolfgang Resch, Mila Jankovic, Thiago Oliveira, Arito Yamane, Hirotaka Nakahashi, Michela Di Virgilio, Anne Bothmer, Andre Nussenzweig, Davide F. Robbiani et al. Translocation-Capture Sequencing Reveals the Extent and Nature of Chromosomal Rearrangements in B Lymphocytes. Cell, 30 September 2011; 147(1) pp. 95 - 106 DOI: 10.1016/j.cell.2011.07.048

Cite This Page:

NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. "New technique identifies first events in tumor development." ScienceDaily. ScienceDaily, 29 September 2011. <www.sciencedaily.com/releases/2011/09/110929144711.htm>.
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2011, September 29). New technique identifies first events in tumor development. ScienceDaily. Retrieved January 29, 2015 from www.sciencedaily.com/releases/2011/09/110929144711.htm
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. "New technique identifies first events in tumor development." ScienceDaily. www.sciencedaily.com/releases/2011/09/110929144711.htm (accessed January 29, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, January 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are We Winning The Fight Against Ebola?

Are We Winning The Fight Against Ebola?

Newsy (Jan. 29, 2015) The World Health Organization announced the fight against Ebola has entered its second phase as the number of cases per week has steadily dropped. Video provided by Newsy
Powered by NewsLook.com
Measles Scare Sends 66 Calif. Students Home

Measles Scare Sends 66 Calif. Students Home

AP (Jan. 29, 2015) Officials say 66 students at a Southern California high school have been told to stay home through the end of next week because they may have been exposed to measles and are not vaccinated. (Jan. 29) Video provided by AP
Powered by NewsLook.com
Group Encourages Black Moms to Breastfeed

Group Encourages Black Moms to Breastfeed

AP (Jan. 29, 2015) A grassroots effort is underway in several US cities to encourage more black women to breastfeed their babies by teaching them the benefits of the age-old practice, which is sometimes shunned in African-American communities. (Jan. 29) Video provided by AP
Powered by NewsLook.com
Sugary Drinks May Cause Early Puberty In Girls, Study Says

Sugary Drinks May Cause Early Puberty In Girls, Study Says

Newsy (Jan. 28, 2015) Harvard researchers found that girls who consumed more than 1.5 sugary drinks a day had their first period earlier than those who drank less. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins