Epigenetics News

Cause For Concern in Microarray-Based Studies

Jan 22, 2007 cancer, news links, research articles

New research published in the Journal of the National Cancer Institute shows that many microarray-based cancer studies have critical flaws in their analyses or conclusions.

In the study, Simon and his NCI colleague Dr. Alain Dupuy looked at 90 studies published through the end of 2004 that compared microarray profiling with medical results. The most frequently studied cancers were blood malignancies (24 studies), lung tumors (12 studies), and breast cancer (12 studies).

Simon and Dupuy then specifically looked at the statistical methods and reporting in 42 studies published in 2004. Half of these efforts had at least one basic error. In the 23 studies with an outcome-related gene finding, nine involved inadequate, confusing, or unstated methods to account for false-positive results, Simon and Dupuy found.

In 13 studies, there were unsupported claims of meaningful classifications of results, where the authors did not do adequate analyses to reach their conclusions. In addition, in the 28 studies that predicted outcomes, 12 used biased estimates of the accuracy of their predictions, according to Simon and Dupuy.

Link

Monday Morning Carnivals and Links

Jan 22, 2007 news links

There are a number of recent science blog carnivals and other reading material that I’d like to highlight:

• Tangled Bank #71
• Mendel’s Garden
• Carnival of Education #102
• Four Stone Hearth #7
• This past weekend marked the 2007 North Carolina Science Blogging Conference, which was attended by nearly 200 researchers, bloggers, students, press, etc. Bora Zivkovic, one of the organizers of the event, has a page devoted to tracking all of the coverage of the event, including the live blogging done at the conference and post-conference articles.
• The National Institutes of Health has opened the NIH VideoCasting site, where everyone can view both past and live seminars and other talks from the NIH. There are 3,222 past events currently on file, organized by topic areas such as Current Topics in Genome Analysis, DNA Repair, and Systems Biology (HT: Genetics and Health).

Shirley Tilghman Wins GSA Medal

Jan 20, 2007 imprinting, news links, research articles

Princeton University President Shirley M. Tilghman has been awarded the Genetics Society of America Medal, which recognizes a scientist’s outstanding contributions to genetics over the past 15 years.

Tilghman was nominated for her pioneering work in epigenetics and imprinting, which has expanded the knowledge base about embryo development in mammals.

Tilghman published many papers characterizing the imprinted H19 and IGF2 genes, many of which can be seen here.

Jane Gitschier interviewed Shirley Tilghman last year in an article for PLoS Genetics. Link

Tumor-Free Breast Tissue Can Have Increased Methylation

Jan 19, 2007 cancer, methylation, news links, research articles

New research from a team at the Ohio State University Comprehensive Cancer Center shows that normal breast tissue as much as 4 cm away from a cancerous breast tissue can have increased methylation in the RASSF1A gene promoter.

During this study, the researchers measured the degrees of methylation in tissue removed from 47 patients who had undergone mastectomies for a form of breast cancer called invasive ductal carcinoma. This tissue was compared with 69 samples of normal tissue taken up to four centimeters (almost two inches) from the tumor’s visible edge and with control tissues removed during breast-reduction surgery.

The study also included two double-mastectomy cases in which both breasts had been removed to prevent cancer recurrence. For these, the researchers also tested tissue from four locations on the breast that had no visible tumor.

The researchers used microdissection techniques to isolate tiny milk ducts in each sample. They then measured methylation levels in the RASSF1A gene in epithelial cells that lined the ducts. These cells were the sources of the initial tumor.

As expected, tumor cells showed the highest methylation levels. But the researchers found significant methylation levels in normal tissue adjacent to the tumors in 29 patients. The degree of methylation was lower than in the tumor cells, but it was 1.75 times higher than in control cells.

“In both double-mastectomy cases, we were surprised to find high methylation levels in the tumor-free breast,” says Yan.

In addition, the researchers identified three other genes (called CYP26A1, KCNAB1 and SNCA) that were highly methylated in about one-third to nearly one-half of the breast tumors.

“Again to our surprise, we found that in 70 percent of cases, when these genes were highly methylated in tumor cells, they were also highly methylated in the adjacent normal tissue,” says Yan.

“This suggests that the presence of DNA methylation in normal tissue adjacent to tumors is more prevalent that previously thought.”

Link

The Just Science Challenge: We Accept

Jan 17, 2007 commentary, news links, site news

There is a movement afoot, known as the Just Science Challenge, that aims to have science bloggers post only about science for the week beginning Monday, February 2 and ending Sunday, February 8.

During that time each blogger should post about science only, with at least one post per day. Furthermore, issues which are favored by anti-scientific groups (creationism, global warming, etc.) should be either avoided, or discussed without reference to anti-scientific positions.

Since the challenge calls for at least one post per day and this site’s curator is a full-time student, half-time researcher, full-time husband and father, I have asked Stephen Rekow (aka Shane) to assist with the week-long event. (I just realized that Mr. Rekow has all of those same responsibilities, plus his son is much younger than my 13-year-old. Good thinking, Trevor.) Shane is also an undergraduate researcher at WSU, and has been working at the lab and on our project for much longer than I have. You should go ahead and jot down his name if you’re a researcher looking for molecular biology grad students. His publications, oral presentations of research, and awards/scholarships as an undergrad are nearly unheard of, and he will most likely teach your postdocs a few things about good wet lab work.

With that said, we plan on covering some of the latest epigenetics research articles, and will most likely traverse some terrain that this site has never been across before (such as the wide world of epigenetics research in plants). Hopefully these posts will be informative and educational for both the students (that would be us) and the readers (that would be you).

If you write a science blog, I would encourage you to accept the challenge. So far, it looks like the following blogs have also accepted the challenge:

• Gene Expression
• Discovering Biology in a Digital World
• My Biotech Life
• Public Rambling
• I’m a chordata, urochordata

Link

Nygaard Named New CEO of Epigenomics AG

Jan 17, 2007 investors, news links

Epigenomics AG (Frankfurt: ECX) has appointed its new CEO: Geert Walther Nygaard, formerly managing director and member of the management board of pharmaceutical and diagnostics company Abbott GmbH & Co. KG.

Nygaard started his career in Denmark, working for Diagnostics companies Beckman Instruments and Dako A/S in national and international positions. He joined Abbott in 1999 as the company’s Country Manager in Denmark from a position as Managing Director of Dako AG in Switzerland. He then moved on into positions with increasing responsibilities, including business development and marketing for Abbott Diagnostics in Europe.

The Science Blogging Anthology 2006

Jan 16, 2007 commentary, news links

Bora Zivkovic of A Blog Around the Clock has announced the release of The Open Laboratory: The Best Writing on Science Blogs 2006. The inaugural anthology hopes to capture the best that the science blogosphere offered in 2006, and the results are pretty impressive. Even more impressive is the fact that Bora had only three weeks from conception to print. It’s no surprise that most are calling for him to edit the anthology’s second edition.

Some of my favorites from the book include It’s not just the genes, it’s the links between them (Pharyngula) and the best and worst parts of scientific life (The Daily Transcript).

Epigenetics Gordon Conference in August 2007

Jan 11, 2007 news links

The 2007 Epigenetics Gordon Conference, held every odd year at the Holderness School in Plymouth, NH, is set for August 5-10, 2007. This year’s conference will be chaired by Dr. Anne-Ferguson Smith of the University of Cambridge and Dr. Steven E. Jacobsen of the University of California, Los Angeles (UCLA). The list of confirmed speakers and chairs:

Histone modifications and variants
Chair: Sarah Elgin
Speakers: Steve Henikoff, Hiten Madhani, Karolin Luger, Terry Magnuson, Justin Goodrich

The dynamic nucleus
Chair: Jasper Rine
Speakers: David Spector, Edith Heard, Peter Fraser, En Li, Vincenzo Pirotta, Ting Wu

Epigenomics
Chair: Steve Jacobsen
Speakers: Bradley Bernstein, Ian Dunham, Rob Martienssen, Peter Jones

The roles of RNA I & II
Chair: Bill Kelly
Speakers: Marjori Matzke, David Baulcombe, Phillip Zamore, Bob Kingston, Vikki Chandler, Craig Pikaard, Shiv Grewal, Denise Barlow

DNA methylation
Chair: Jörn Walter
Speakers: Eric Selker, Tim Bestor, Hiro Sasaki, Judy Bender, Xiaodong Cheng

Imprinting, dosage compensation and chromosomal mechanisms
Chair: Emma Whitelaw
Speakers: Ueli Grossniklaus, Marisa Bartolomei, Jeannie Lee, Barbara Meyer, Jim Birchler

Epigenetics in developmental processes
Chair: Tomoko Kaneko-Ishino
Speakers: Renato Paro, Rudolph Jaenisch, Laura O’Neill, Azim Surani, Wolf Reik

Epigenetics and disease
Chair: Amar Klar
Speakers: Olivier Voinnet, Asifa Akhtar, Steve Baylin, Mike Higgins

Epigenetics, environment and evolution
Chair: Jean Finnegan
Speakers: Phil Avner, Eric Richards, Rick Amasino

Applications for the conference must be submitted by July 15, 2007. Applicants are encouraged to apply early as the selection of participants and short talks will commence in March 2007. Link

Results of Clinical Trial in Blood-Based Cancer Detection

Jan 11, 2007 cancer, methylation, news links

BioCangen Inc. has announced the initial results of its clinical validation study of early cancer detection.

Among the blood samples from 102 patients with solid tumors including lung cancer, colon cancer, breast cancer and stomach cancer, 73 samples were correctly identified as the cancer, showing a 71.6% detection sensitivity. Among the 82 health individuals, only 3 samples were identified as the cancer, indicating a 96.3% specificity.

These results will be further validated with multi-center trials for submission to the FDA. Link

Illumina Introduces High Throughput DNA Methylation Profiling

Jan 10, 2007 cancer, methylation, news links

Illumina Inc. (NASDAQ:ILMN) has announced that it has introduced a high-throughput DNA methylation profiling technology capable of surveying up to 1,536 methylation sites across 96 samples simultaneously. From Business Wire:

By pairing Illumina’s proven BeadArray platform with the GoldenGate(R) assay approach, researchers have the ability to perform genome-wide methylation profiling across multiple areas such as cancer and human embryonic stem cell research. The GoldenGate Methylation Cancer Panel I, the first standard panel, covers 1,505 methylation sites over 800 cancer genes. Custom-content methylation panels will soon be available to meet individual research needs.

Recently, the NCI and the National Human Genome Research Institute (NHGRI) announced two more components of The Cancer Genome Atlas (TCGA) Pilot Project, a three-year, $100 million collaboration established to test the feasibility of using large-scale genome analysis technologies to identify important genetic changes involved in cancer. As part of this project, the Sidney Kimmel Comprehensive Cancer Center of the Johns Hopkins University and the Norris Comprehensive Cancer Center of the University of Southern California were awarded funds to establish Cancer Genome Characterization Centers (CGCC). At these centers, researchers will utilize Illumina’s GoldenGate methylation technology to detect changes in methylation profiles associated with transcribed genes in cancer samples.

Link

Final Report Approved for Large U.S. Population Cohort Project

Jan 8, 2007 news links

In November 2006, the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) met to discuss and approve the final version of their report on policy issues associated with undertaking a large U.S. population cohort project on genes, environment, and disease. Our previous coverage of this project, including a brief summary of the project’s history and scope, can be found here.The task force that spearheaded work on the report was led by Dr. Huntington F. Willard, Director of the Institute for Genome Sciences & Policy at Duke University Medical Center. Dr. Willard began his presentation before the committee with a brief introduction regarding the project:

For those who are new to this, the issue at hand is to examine issues relevant to a possible United States large population study which we define in this report as an approach to learning more about relationships among genes, the environment, and common disease. And the goals of the studies, both ones ongoing and ones planned both in this country and elsewhere, are to determine mechanisms underlying common complex diseases to inform treatment and prevention strategies and ultimately, of course, to improve health in this country and elsewhere.

Following a half-day session discussing the fine details of the report, including suggested revisions to wording and substantial additions following review of public comments, the committee voted unanimously to approve the final report and send it to the Secretary of Health and Human Services on or around January 1, 2007. Transcripts and video webcasts of the committee’s 2-day meeting are available online. Link

Links for a Windy Sunday Afternoon

Jan 7, 2007 commentary, news links

It’s Sunday afternoon, the roads are covered in a slick, slushy melting snow that doesn’t make for easy driving, and it seems like a good time to share links to some good science writing.

• Viva La Evolucion! hosts Tangled Bank #70, a collection of the blogosphere’s best science writing over the past few weeks.
• Cells Weekly #11, a summary of cellular and molecular biology posts from the past week, is available at Migrations.
• Congressional Budget Delay Stymies Scientific Research (New York Times).

Epigenetics Garners Fifth Spot in Discover’s Top Science Stories of 2006

Jan 6, 2007 cancer, environmental alterations, methylation, news links

Discover Magazine has recognized several related discoveries in the field of epigenetics as the fifth top science story of 2006. The article details the research of Dr. Minoo Rassoulzadegan at the University of Nice:

Minoo Rassoulzadegan’s mice are unruly. In blatant violation of the laws of genetics—described a century ago by famed monk-scientist Gregor Mendel—they inherit their parents’ coloring without inheriting the genes that cause it.

Rassoulzadegan stumbled upon her rodent scofflaws after altering a gene in gray mice so that their feet and the tips of their tails turned white. The big surprise came in the next generation. Some offspring also had white spots, even though they didn’t inherit the mutated gene and so should have been all gray. When she looked for the cause, Rassoulzadegan found unusual amounts of RNA in the sperm of the mutant parents. She then injected RNA from the brains and sperm of those mice into ordinary gray mouse embryos. Many of the RNA-injected embryos likewise grew into white-tailed adults, regardless of the coloration written in their DNA.

The article also highlights the research of Dr. Vicki Chandler of the University of Arizona at Tucson and Dr. Michael Skinner of Washington State University. Link

Biomarkers In Focus At Environmental Health Perspectives

Jan 2, 2007 environmental alterations, methylation, news links

The Focus article in the December issue of Environmental Health Perspective covers a term that should be very familiar to anyone following epigenetics: biomarker. While the term “biomarker” can be used to mean many different things, there are actually clear definitions for biomarkers that have been designated by scientists:

In 1987, the National Research Council convened a committee to investigate how biomarkers were being developed and used in the environmental health sciences. The conclusions were documented in a seminal paper published in the October 1987 issue of EHP, which described the four basic biomarker groupings still in use today: exposure biomarkers (which include markers of external exposure and of internal dose); biomarkers of biologically effective dose; effect biomarkers (which include markers of health impairment or recognized disease, early disease precursors, or peripheral events that predict health impairment); and susceptibility biomarkers (which include intrinsic genetic or other characteristics or preexisting diseases that result in an increase in internal dose, biologically effective dose, or target tissue response).

One of the common ways that epigenetic researchers aim to identify a biomarker for a particular disease or phenotype is by measuring DNA methylation on specific gene promoters of interest — whether it be hypermethylation (an increase in DNA methylation) or hypomethylation (a decrease in DNA methylation). However, as the mechanism for linking a change in DNA methylation with disease susceptibility are not understood, there seems to be no clearly defined method for identifying an epigenetic biomarker using DNA methylation. Some researchers use a method that measures the percentage of methylated CG sites within a particular loci, while others examine specific CG sites and determine if any specific CG site’s methylation status is changed. These differing approaches, while both potentially useful in identifying changes in methylation pattern, may be a source of conflicting results in epigenetics research and could lead to a loss of confidence in using DNA methylation as a means of identifying clinically important biomarkers for disease. Link

Was 2006 a Good Year for Epigenetics? (Part II)

Dec 31, 2006 cancer, commentary, environmental alterations, imprinting, methylation, news links, research articles

In an earlier post, I began taking a look back at the year 2006 in epigenetics. With the last day of 2006 upon us, it seemed like a good time to complete the review of the year’s most memorable events (covered by Epigenetics News).

• There were key advances using epigenetics to improve the detection of certain cancers, including prostate, breast and colorectal cancer.
• The journal Nature drew a fresh audience to the topic of epigenetics with the article Epigenetics: Unfinished Symphony.
• The first hypomethylating drug, Dacogen, was approved by the Food and Drug Administration for the treatment of myelodysplastic syndromes.
• The epigenetic map of human chromosomes 6, 20, and 22 was released.
• The Secretary’s Advisory Committee on Genetics, Health, and Society released a draft report for public comment on the potential U.S. population cohort study on genes, environment, and disease.
• Epigenetics was put in an evolutionary perspective.
• We hosted our first carnival, Tangled Bank #61.
• A CpG methylation system was discovered in the western honey bee.
• Epigenetics was linked as a potential factor in adult-onset disease.
• A test was developed to analyze methylation using a breath sample.

This is just a sample of what was covered in 2006. Look for even more coverage of everything epigenetics in 2007.