Featured Research

from universities, journals, and other organizations

Key Mechanism That Occurs At Inception Point Of Many Human Lymphomas Identified

Date:
December 16, 2008
Source:
University of Southern California
Summary:
Researchers have explained how certain key mutations occur in human lymphomas -- a process that has, until now, remained a mystery.

Researchers at the Keck School of Medicine of the University of Southern California (USC) have explained how certain key mutations occur in human lymphomas—a process that has, until now, remained a mystery.

The findings of the study will have a significant impact on future study of how human lymphoma occurs.

Chromosomal translocations, in which segments of DNA are moved around the genome, are DNA mutations frequently found in blood cancers. They occur when two chromosomes break and the resulting fragments are reassembled in an exchange, says Michael R. Lieber, M.D/Ph.D., Rita and Edward Polusky Professor in Basic Cancer Research at the Keck School of Medicine and the study's principal investigator.

"Our study provides new insight into understanding how these translocations occur and describes a key and informative fingerprint at these chromosomal break sites," Lieber says.

The fingerprint had been overlooked for decades because chromosomal break sites typically suffer damage that obscures the fingerprint, he says.

"The precise steps leading to this pathologic rearrangement process—especially how the DNA is broken—have been a mystery for 25 years, in large part because these events occur long before the cancer becomes clinically apparent, and conventional experimental techniques do not reflect the process as it occurs naturally," says Albert Tsai, M.D/ Ph.D. candidate at the Keck School of Medicine and the lead author of the study.

Expanding on previous work done at the Keck School and USC Norris Comprehensive Cancer Center and elsewhere, researchers studied patient tumor chromosomal translocations to gain an important clue as to how the most common lymphomas are caused. The study demonstrated that these breaks are focused at CpG sites, short special sequences in the genome, within restricted breakage zones. The CpG localization occurs in early B-cells, but not in translocations before or after that stage.

Their findings implicated roles for two enzymes—AID and RAG complex—which are normally present in lymphocytes and that function to diversify the immune system to defend against attack by bacteria, viruses and parasites, Lieber says. The diversification process involves altering the DNA which encodes antibodies, by cutting and rejoining the DNA in a way that sometimes goes awry. This appears to be what causes the chromosomal translocations, he says.

"Based on previous clues, we did a number of biochemical studies to verify our hunch about the mechanism of translocation," Lieber says. "Our study demonstrates the biochemical feasibility of the sequence of events proposed, and this matches the fingerprint left by the chromosomal translocations."

The study relied on an important collaboration with Chih-Lin Hsieh, Ph.D., Catherine & Joseph Aresty Chair in Urologic Research at the Keck School of Medicine, and Markus Muschen, M.D., associate professor of pediatrics, biochemistry and molecular biology at the Keck School and director of the Leukemia Research Program at Childrens Hospital Los Angeles.

The study was funded by the National Cancer Institute and the National Institute of General Medical Sciences.


Story Source:

The above story is based on materials provided by University of Southern California. Note: Materials may be edited for content and length.


Journal Reference:

  1. Albert G. Tsai, Haihui Lu, Sathees C. Raghavan, Markus Muschen, Chih-Lin Hsieh and Michael R. Lieber. Human Chromosomal Translocations at CpG Sites and a Theoretical Basis for their Lineage and Stage Specificity. Cell, D-08-00489R3

Cite This Page:

University of Southern California. "Key Mechanism That Occurs At Inception Point Of Many Human Lymphomas Identified." ScienceDaily. ScienceDaily, 16 December 2008. <www.sciencedaily.com/releases/2008/12/081211141942.htm>.
University of Southern California. (2008, December 16). Key Mechanism That Occurs At Inception Point Of Many Human Lymphomas Identified. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2008/12/081211141942.htm
University of Southern California. "Key Mechanism That Occurs At Inception Point Of Many Human Lymphomas Identified." ScienceDaily. www.sciencedaily.com/releases/2008/12/081211141942.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. 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:
from the past week

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