Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Shortened chromosomes linked to early stages of cancer development

27.05.2004


Scientists at the Johns Hopkins Kimmel Cancer Center say they have evidence that abnormally short telomeres - the end-caps on chromosomes that normally preserve genetic integrity -appear to play a role in the early development of many types of cancer.



"Cancer researchers have debated whether shortened telomeres were a cause or effect of tumors," says Alan K. Meeker, Ph.D., lead author of the study and a postdoctoral fellow in urology and pathology at Hopkins. "What our study suggests is that telomere dysfunction may be a key component in the development of many epithelial cancers, those that arise from tissues lining our organs."

Studying tissue taken from small precancerous lesions in the bladder, esophagus, large intestine, mouth and cervix, the research team found abnormal telomere lengths in 97 percent of the cases examined. In particular, abnormally short telomeres were found in 88 percent of cases.


"We were surprised how often you see shortened telomeres this early in the development of these cancers," says Meeker. "It’s a strong indicator that abnormal telomeres are likely playing a causal role in cancer development."

Telomeres cap the chromosome ends, protecting the interior, gene-containing parts of the chromosome from being accidentally lost. As normal cells divide and age, some of the telomere DNA is lost, and the telomeres get progressively shorter. Normal cells monitor the lengths of their telomeres and initiate cell suicide or halt cell division when telomeres get too short. Other researchers have shown in mice that cancer, which is characterized principally by unrestricted cell growth and lack of cell death, can occur if this monitoring system breaks down, leading to the development of chromosomal abnormalities.

"It appears that the telomere shortening frequently observed in large advanced tumors has already occurred before it can be detected by standard diagnostic tools, when cellular changes characteristic of early precancer can only be seen through a microscope by a pathologist," says Angelo M. De Marzo, M.D., Ph.D., senior author of the study and associate professor of urology, pathology and oncology at Johns Hopkins. "Therefore, intervention strategies aimed at preventing, or even reversing, telomere shortening may be effective in lowering cancer incidence. And assessing telomere length may provide a new direction for cancer prevention studies, and lead to improved early diagnosis of precancerous lesions."

For the study, published in the May 15 issue of the journal Clinical Cancer Research, Meeker, De Marzo and colleagues used a technique called fluorescent in situ hybridization (FISH) to compare telomere length in cells from both precancerous lesions and normal surrounding cells of the bladder, esophagus, large intestine, mouth and cervix.

The FISH test uses fluorescent-labeled probes specific for particular locations in DNA and is commonly used to detect or confirm gene or chromosome abnormalities. Chromosomal DNA is first denatured, a process that separates the strands within the DNA’s double helix structure. The Hopkins scientists then added a fluorescent probe specific for telomere regions. As the DNA re-forms into a double helix, it blends with the fluorescent molecules, enabling scientists to examine specific chromosomal locations under a microscope for the level of fluorescence that corresponds to telomere length.

Not all precancerous epithethial lesions are capable of fully advancing to malignant cancers, Meeker says. One reason for this may be that if genetic instability gets too high, the cells die, thus blocking cancer progression. Only cells that find a way to balance their telomere length - allowing unlimited cell division and a limited degree of genomic stabilization - can progress to becoming an invasive, life-threatening tumor.

The Hopkins research team examined 35 precancerous lesions from 25 patients, including 11 lesions from eight bladders, three lesions from three uterine cervixes, seven lesions from five large intestines, six lesions from three esophagi and eight lesions from six mouths. They scored the telomere lengths on a five-point scale ranging from very short to very long.

Overall, the group found telomere length abnormalities in 34 of 35 lesions studied (97 percent). Short or very short telomeres were observed in all lesions of the esophagus, large intestine and uterine cervix; in eight of 11 (72 percent) lesions of the bladder; and in seven of eight lesions of the oral cavity, which includes the mouth and throat. Ten of 35 (29 percent) lesions, particularly those of the bladder, displayed a variety of telomere lengths.

More than one million human epithelial cancers are diagnosed every year, Meeker says, and these cancers cause a half-million deaths each year.

Previous studies by the research team and others at Johns Hopkins found shortened telomeres in more than 90 percent of precancerous lesions of the prostate, pancreas and breast.


The current study was funded by the U.S. Public Health Service. Coauthors were Jessica L. Hicks, Christine A. Iacobuzio-Donahue, Elizabeth A. Montgomery, William H. Westra, Theresa Y. Chan and Brigitte M. Ronnett.

Meeker, Alan K., et al, "Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis," Clinical Cancer Research, May 15, 2004, Vol. 10, Issue 10.

Vanessa Wasta | EurekAlert!
Further information:
http://clincancerres.aacrjournals.org
http://www.hopkinskimmelcancercenter.org/

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>