Navigation Links
Johns Hopkins scientists expose cancer cells' universal 'dark matter'

Using the latest gene sequencing tools to examine so-called epigenetic influences on the DNA makeup of colon cancer, a Johns Hopkins team says its results suggest cancer treatment might eventually be more tolerable and successful if therapies could focus on helping cancer cells get back to normal in addition to strategies for killing them.

In a report published June 26 in Nature Genetics, the investigators focused on a particular epigenetic biochemical signature known as methylation, which silences genes. Although not part of a gene's central DNA sequence, it is copied when a cell divides, perpetuating its activity.

By comparing the epigenomes of eight human tissue samples -- three from noncancerous colon tissue, three from colon tumors and two from polyps (early-stage colon cancer) -- the team found that in all the colon tumors the defining characteristic was a universally "chaotic" pattern of methylation. In noncancerous tissue, they found methylation occurring in well-defined places, either as small "islands" of methylation or huge methylated "blocks" that collectively encompassed at least a third of the genome.

"In the cancer tissue we saw that the once-precise boundaries of the islands had shifted or disappeared altogether, and the start and end points of the sites appeared unregulated," says Andrew Feinberg, M.D., M.P.H., professor of molecular medicine and director of the Center for Epigenetics at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences. "We also saw a loss of methylation, presumably increasing the randomness of gene function within them."

"What seems to define cancer at the epigenetic level may be simple and common, namely chaos that seems to be universal," he adds.

The researchers noted that cells in their normal colon tissue samples stayed methylated at around the 80 percent level for large (and previously unexamined) blocks of the epigenome. By comparison, cells from colon tumors comprising those same huge blocks had no such stability and were much more variable in terms of methylation levels.

Feinberg says the findings could mean that current efforts to simply identify methylation markers as signals of cancer or targets of cancer therapy may be misleading or worse, won't do the job at all. An alternative would be a new method that detects epigenetic chaos universally in any cancer epigenome.

The team designed a custom test to compare about 20 noncancerous tissue samples to 20 samples from each of a variety of tumors as they investigated thousands of methylation sites for colon, breast, lung, kidney and thyroid cancers. They found that, here again, methylation was well-regulated in the normal tissues, almost always occurring within a limited range of variability. However, in the very same specific places of the epigenome characterized by chaos in colon cancer cells, all the other cancerous tissues examined by the team showed distinctly variable and "chaotic" levels of methylation variation.

"Maybe the big lesson learned from our observation of this universal chaos is that we may need to think not so much about just killing cancer cells, but also about ways of helping cancer cells figure out how to be what they're supposed to be, and re-educate them so they can stay truer to their normal identities," Feinberg says.

From the cancer cells' "perspective," Feinberg says, the chaos is helpful, endowing tumors with the ability to turn genes on and off in an uncontrolled way, and making cancer cells adaptable enough to live in all different kinds of environments, spread and thrive in foreign tissue.

"The regions of epigenetic chaos where methylation appears wildly variable in at least five different common cancers are -- not so coincidentally -- the very same as those that during normal development are important in controlling cell differentiation, or what particular cells are supposed to be, like normal colon cells," Feinberg says.

"The same epigenetic malleability that permits human cells with the same DNA to become different tissue types during development also confers vulnerability," adds Rafael Irizarry, Ph.D., a professor of biostatistics in the Johns Hopkins University Bloomberg School of Public Health, who with Feinberg, led this study. "The epigenome has these regions where change is easy in order for some cells to become kidney and others, brain and spleen, for example, but that very vulnerability to change may ultimately lead to cancer. Targeting those regions might help the cells become more normal."

Because the new study also identifies regions of the genome that appear to control this epigenetic chaos, Feinberg and his team say it may prove potentially fruitful in revealing new targets for cancer therapy or prevention.


Contact: Maryalice Yakutchik
Johns Hopkins Medical Institutions

Related biology news :

1. Johns Hopkins researchers detect sweet cacophony while listening to cellular cross-talk
2. Johns Hopkins scientists pull proteins tail to curtail cancer
3. Case Western Reserve University works with Johnson & Johnson Services Inc. on research grant
4. Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant awarded to Johns Hopkins Early Career investigator
5. Johns Hopkins scientists discover a controller of brain circuitry
6. JDRF announces diabetes research program with Johnson & Johnson
7. Johnson & Johnson award goes to research of the cause of brain cell damage in Parkinsons
8. American Society for Microbiology honors Ryan Johnson
9. UNCs Dr. Sean McLean receives Robert Wood Johnson Foundation award
10. Johns Hopkins researchers reshape basic understanding of cell division
11. Encyclopedia of Life names Dr. Rebecca Johnson a 2011 Rubenstein Fellow
Post Your Comments:
(Date:11/17/2015)... Paris , qui ... Paris , qui s,est tenu du ... leader de l,innovation biométrique, a inventé le premier scanner ... sur la même surface de balayage. Jusqu,ici, deux scanners ... les empreintes digitales. Désormais, un seul scanner est en ...
(Date:11/12/2015)... , Nov. 12, 2015  Arxspan has entered ... MIT and Harvard for use of its ArxLab ... management tools. The partnership will support the institute,s ... and chemical research information internally and with external ... used for managing the Institute,s electronic laboratory notebook, ...
(Date:11/9/2015)... DUBLIN , Nov. 09, 2015 /PRNewswire/ ... announced the addition of the "Global ... to their offering. --> ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , Nov. 25, 2015 Orexigen® Therapeutics, ... will participate in a fireside chat discussion at the ... New York . The discussion is scheduled for ... .  A replay will be available ... Contact:McDavid Stilwell  , Julie NormartVP, Corporate Communications and ...
(Date:11/24/2015)... ... November 24, 2015 , ... The United States Golf Association (USGA) ... USGA Green Section Award. Presented annually since 1961, the USGA Green Section Award recognizes ... with turfgrass. , Clarke, of Iselin, N.J., is an extension specialist of ...
(Date:11/24/2015)... ... 24, 2015 , ... Copper is an essential micronutrient that ... proteins, copper is also toxic to cells. With a $1.3 million award from ... conduct a systematic study of copper in the bacteria Pseudomonas aeruginosa (P. aeruginosa), ...
(Date:11/24/2015)... India , November 24, 2015 ... a new market research report "Oligonucleotide Synthesis Market by ... Application (PCR, Gene Synthesis, Diagnostic, DNA, RNAi), End-User (Research, ... 2020", published by MarketsandMarkets, the market is expected to ... Million in 2015, at a CAGR of 10.1% during ...
Breaking Biology Technology: