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 Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

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: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>