Featured Research

from universities, journals, and other organizations

Evolutionary Genetic Tools Trace Cancer Clone Lines

Date:
June 18, 1999
Source:
University Of Southern California
Summary:
Sophisticated computational tools developed to trace species evolution by comparing DNA sequences have now been used to track the development of human cancer.

Sophisticated computational tools developed to trace species evolution by comparing DNA sequences have now been used to track the development of human cancer.

The collaboration by a USC team led by cancer researcher Darryl Shibata and computational biologist Simon Tavare casts doubt on conventional wisdom regarding the relationship between colorectal cancers (carcinomas) and the polyps (adenomas) which typically precede them.

The preliminary findings, if they can be confirmed, may have clinical significance in considering non-surgical options for treating polyps.

According to Shibata, an associate professor in the USC medical school department of pathology, oncologists have long believed that the development of colon cancer is a progressive and linear process, with a normal cell mutating into adenoma, and the adenoma subsequently mutating further into carcinoma. In this conventional model, the adenoma is the direct precursor or ancestor to the carcinoma.

But according to the new study, published in the June issue of the American Journal of Pathology, genetic evolution analysis indicates that adenoma and carcinoma lines can arise from a common precursor but subsequently develop in parallel. In this scenario, the adenoma is not the "mother" of the carcinoma but rather a cousin.

The finding suggests that the direct progenitor of cancer cells may not be the most prevalent cell in a polyp. The clone comprising the majority of cells in the adenoma is genetically a dead end with respect to the cancer. One important consequence is that in some cases cancer may arise without being preceded by polyps at all, that is, "the true progenitor may be occult," according to Shibata.

The researcher notes that precisely this scenario is sometimes seen when a patient with no symptoms or polyps at one examination is found a year later to have developed colon cancer. Traditionally, it had been thought that the initial examination simply missed finding polyps or that evolution from a polyp to a cancer occurred faster than usual.

The analysis was possible because the abnormal colon cells studied, adenomas and carcinomas alike, all share a specific mutation that destroys the cell's ability to edit and repair errors in DNA replication. As a result, such cells accumulate such errors at a rapid and constant rate.

"This gives us a mutational clock, which we can use to keep track of progressions in the daughter cell lines," says Shibata. The frequency of the changes allows current genetic technology to compare easily cell lines through successive generations in specific non-coding parts of the human genome known as microsatellites.

The genetic sequences analyzed normally change very slowly, and cells from most kinds of cancer wouldn't be expected to accumulate many changes in the lifetime of their human hosts. But such changes do occur and accumulate in successive generations of normal cells over geologic time. This is where Tavare, the George and Louise Kawamoto Chair In Biological Sciences and professor of mathematics in USC's college of letters, arts & sciences, had learned to analyze them to study the history of species.

As the universal informational molecule, DNA sequences can be analyzed and compared regardless of their origins. "While changes that would normally accumulate over millennia in normal cells accumulate over months in these mismatch repair deficient tumor cells," says Tavarι, "they can be analyzed using similar mathematical techniques."

The analysis, done on a number of cell samples from three different patients, shows that, at least in this group of samples, the carcinoma cells and adenoma cells had diverged far back in the cell lineage, long before carcinoma was seen.

Because polyps are routinely removed when found, the findings don't suggest great changes in clinical approach to disease, says Shibata "as physical removal would eliminate both occult and overt potential cancer precursors. However, attempts to shrink polyps with chemotherapy may not prevent cancer," since if the new analysis is correct, reductions in the sizes of polyps may reflect efficacy against the adenoma dead-ends and not in the extinction of the actual cancer lineage.

Shibata began the research after reading about work in computational biology and thinking that the techniques might be applicable to oncology, made contact with Tavare, an international authority on development of computational techniques in molecular evolution.

Extensive meetings were necessary to make the experiment work: "He knew so little about the way tumors grow, and I knew so little about his methods," said Shibata.

However, Shibata hopes to continue to work with Tavare and others to refine his technique to attempt to shed light on development of metastases, the deadly colonies sent out by initial growths. They want to ask, are these descendents of the early cancer line or are they only produced at a late stage of tumor development?

Shibata notes that current techniques can take advantage of powerful animal models, although "mice don't live long enough to match the time scale of human tumor evolution" he said.

But he is excited by the prospects opened by the work, which he says is the first time the full sophistication of the techniques developed to track evolutionary changes have been used to study cancers.

Collaborating with Shibata and Tavare were Jen-Lin Tsao of the USC Norris Cancer Center department of pathology, Reijo Salovaar and Lauri Aaltonen of the University of Helsinki department of pathology and medical genetics, Helsinki, Finland; and Jeremy R. Jass, of the University of Queensland, Medical School, Herston, Australia.

The research was supported by grants from the National Institutes of Health and the National Science Foundation.


Story Source:

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


Cite This Page:

University Of Southern California. "Evolutionary Genetic Tools Trace Cancer Clone Lines." ScienceDaily. ScienceDaily, 18 June 1999. <www.sciencedaily.com/releases/1999/06/990618063559.htm>.
University Of Southern California. (1999, June 18). Evolutionary Genetic Tools Trace Cancer Clone Lines. ScienceDaily. Retrieved September 1, 2014 from www.sciencedaily.com/releases/1999/06/990618063559.htm
University Of Southern California. "Evolutionary Genetic Tools Trace Cancer Clone Lines." ScienceDaily. www.sciencedaily.com/releases/1999/06/990618063559.htm (accessed September 1, 2014).

Share This




More Health & Medicine News

Monday, September 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) — A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) — Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) — California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
New Drug Could Reduce Cardiovascular Deaths

New Drug Could Reduce Cardiovascular Deaths

Newsy (Aug. 30, 2014) — The new drug from Novartis could reduce cardiovascular deaths by 20 percent compared to other similar drugs. 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