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:

(Date:11/16/2015)... SAN JOSE, Calif. , Nov 16, 2015 ... leading developer of human interface solutions, today announced ... new Synaptics TouchView ™ touch controller and ... the architectural revolution of smartphones. These new TDDI ... and include TD4100 (HD resolution), TD4302 (WQHD resolution), ...
(Date:11/12/2015)... Mass. , Nov. 12, 2015  Arxspan ... Institute of MIT and Harvard for use of ... discovery information management tools. The partnership will support ... both biological and chemical research information internally and ... will be used for managing the Institute,s electronic ...
(Date:11/11/2015)... 2015   MedNet Solutions , an innovative SaaS-based eClinical ... is pleased to announce that it will be a Sponsor ... event, to be held November 17-19 in Hamburg ... demonstrations of iMedNet , MedNet,s easy-to-use, proven ... has been able to deliver time and cost savings ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... Partnership includes an MPP ... for the u niversity , s Solid ... s cale - up through ... Africa , where licensees based anywhere in the world will have the ... --> Africa , where licensees based anywhere in the world will ...
(Date:11/30/2015)... 30, 2015 Spherix Incorporated (Nasdaq: ... the fostering and monetization of intellectual property, today ... initiatives designed to create shareholder value. ... Spherix. "Based on published reports, the total addressable ... billion and Spherix will seek to secure fair ...
(Date:11/30/2015)... 2015 TapImmune, Inc. (TPIV), ... innovative peptide and gene-based immunotherapeutics and vaccines for the ... will be presenting at the 8 th Annual ... 2.30 PM PT. Dr. John N. Bonfiglio ... giving the presentation and will join TapImmune management in ...
(Date:11/30/2015)... RATON, Florida and MAGDEBURG, Germany ... Congress of NeuroRehabilitation (ECNR) in Vienna, Austria ... 3rd European Congress of NeuroRehabilitation (ECNR) in ... 2015. --> NovaVision, a wholly owned subsidiary of ... the European version of its Internet-delivered NovaVision Therapy Suite at ...
Breaking Biology Technology: