Navigation Links
New view of cancer: 'Epigenetic' changes come before mutations

A Johns Hopkins researcher, with colleagues in Sweden and at the Fred Hutchinson Cancer Research Center, suggests that the traditional view of cancer as a group of diseases with markedly different biological properties arising from a series of alterations within a cell's nuclear DNA may have to give way to a more complicated view. In the January issue of Nature Reviews Genetics, available online Dec. 21, he and his colleagues suggest that cancers instead begin with "epigenetic" alterations to stem cells.

"We're not contradicting the view that genetic changes occur in the development of cancers, but there also are epigenetic changes and those come first," says lead author Andrew Feinberg, M.D., M.P.H., King Fahd Professor of Medicine and director of the Center for Epigenetics in Common Human Disease at Johns Hopkins.

Cells affected by epigenetic changes look normal under a microscope at low levels of resolution, Feinberg says, "but if you look carefully at the genome, you find there are subtle changes." By tracking these changes, he suggests, doctors potentially could treat people before tumors develop in much the same way as cardiologists prescribe cholesterol-lowering drugs to help prevent heart disease.

Epigenetic changes -- those that don't affect the gene's sequence of DNA but change the gene in other ways -- influence a wide variety of human diseases, including cancer, birth defects and psychiatric conditions. Epigenetic alterations include the turning off or quieting of genes that normally suppress cancer and the turning on of oncogenes to produce proteins that set off malignant behavior.

Epigenetic changes are found in normal cells of patients with cancer and are associated with cancer risk, Feinberg notes.

As one example, in a study published in the Feb. 24, 2005, online version of Science, Feinberg and colleagues in the United States, Sweden and Japan reported that mice engineered to have a double dose of insulin-li ke growth factor 2 (IGF2) had more primitive precursor cells in the lining of the colon than normal mice. When these mice also carried a colon-cancer-causing genetic mutation, they developed twice as many tumors as mice with normal IGF2 levels. The extra IGF2 stemmed not from a genetic problem, or mutation, but from an epigenetic problem that improperly turned on the copy of the IGF2 gene that should have remained off.

Feinberg and his colleagues propose that cancers develop via a three-step process. First, there is an epigenetic disruption of progenitor cells within an organ or tissue, altered by abnormal regulation of tumor-progenitor genes. This leads to a population of cells ready to cause new growth.

The second step involves an initiating mutation within the population of epigenetically disrupted progenitor cells at the earliest stages of new cell growth, such as the rearrangement of chromosomes in the development of leukemia. This mutation normally has been considered the first step in cancer development.

The third step is genetic and epigenetic instability, which leads to increased tumor evolution.

Many of the properties of advanced tumors, including the ability to spread, or metastasize, are inherent properties of the progenitor cells that give rise to the primary tumor, Feinberg notes. These properties do not necessarily require other mutations to occur.

"Greater attention should be paid to the apparently normal cells of patients with cancer or those at risk for cancer, as they might be crucial targets for epigenetic alteration and might be an important target for prevention and screening," he says.

Authors on the review are Andrew Feinberg of Johns Hopkins; Rolf Ohlsson of Uppsala University, Sweden; and Steven Henikoff of the Howard Hughes Medical Institute at the Fred Hutchinson Cancer Research Center.


'"/>

Source:Johns Hopkins Medical Institutions


Related biology news :

1. Building a better mouse model of lung cancer: FHIT counts
2. Researchers trace evolution to relatively simple genetic changes
3. Plants defy Mendels inheritance laws, may prompt textbook changes
4. Scientists find evidence of catastrophic sand avalanches, sea level changes in Gulf of Mexico
5. Customized gene chip provides rapid detection of genetic changes in childrens cancer
6. New amphibian species result from exploration, not from rule changes
7. Embryonic stem cells accrue genetic changes
8. Meditation associated with structural changes in brain
9. Bird song changes sound alarm over habitat fragmentation
10. Ocean dead zones trigger sex changes in fish, posing extinction threat
11. Genome changes tracked during multiple myeloma initiation, progression and treatment
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/18/2017)... April 18, 2017  Socionext Inc., a global expert in SoC-based ... edge server, the M820, which features the company,s hybrid codec technology. ... by Tera Probe, Inc., will be showcased during the upcoming Medtec ... show at the Las Vegas Convention Center ... Click here ...
(Date:4/11/2017)... 11, 2017 Crossmatch®, a globally-recognized leader ... today announced that it has been awarded a ... Activity (IARPA) to develop next-generation Presentation Attack Detection ... "Innovation has been a driving force within Crossmatch ... allow us to innovate and develop new technologies ...
(Date:4/6/2017)... April 6, 2017 Forecasts by ... Document Readers, by End-Use (Transportation & Logistics, Government & ... Gas & Fossil Generation Facility, Nuclear Power), Industrial, Retail, ... Are you looking for a definitive report ... ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... AMRI, ... and biotechnology industries to improve patient outcomes and quality of life, will now ... testing are being attributed to new regulatory requirements for all new drug products, ...
(Date:10/11/2017)... ... ... a basic first aid supply for any work environment, but most personal eye wash can ... a dangerous substance enters both eyes? It’s one less decision, and likely quicker response time ... , “Whether its dirt and debris, or an acid or alkali, getting anything in your ...
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. 11, ... Research, London (ICR) and University of ... SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma (MM), ... nine . The University of Leeds ... funded by Myeloma UK, and ICR will perform the testing ...
(Date:10/10/2017)... , ... October 10, 2017 , ... San Diego-based team ... its corporate rebranding initiative announced today. The bold new look is part of ... the company moves into a significant growth period. , It will also expand its ...
Breaking Biology Technology: