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


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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).

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

Methylation Markers Found for Multiple Cancers


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A research group at University of Texas Southwestern have discovered multiple genes that are consistently methylated in lung, breast, colon, and prostate cancers. The research from Shames et. al was published this week in PLoS Medicine: A Genome-Wide Screen for Promoter Methylation in Lung Cancer Identifies Novel Methylation Markers for Multiple Malignancies.

    The researchers used microarray expression profiling to examine gene expression patterns in several lung cancer and normal lung cell lines. In this technique, labeled RNA molecules isolated from cells are applied to a “chip” carrying an array of gene fragments. Here, they stick to the fragment that represents the gene from which they were made, which allows the genes that the cells express to be catalogued. By comparing the expression profiles of lung cancer cells and normal lung cells before and after treatment with a chemical that inhibits DNA methylation, the researchers identified genes that were methylated in the cancer cells—that is, genes that were expressed in normal cells but not in cancer cells unless methylation was inhibited. 132 of these genes contained CpG islands. The researchers examined the promoters of 45 of these genes in lung cancer cells taken straight from patients and found that 31 of the promoters were methylated in tumor tissues but not in adjacent normal tissues. Finally, the researchers looked at promoter methylation of the eight genes most frequently and specifically methylated in the lung cancer samples in breast, colon, and prostate cancers. Seven of the genes were frequently methylated in both lung and breast cancers; four were extensively methylated in all the tumor types.
Link

A Point of Clarification


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I have received many e-mails from readers, authors, investors, consultants, and others related to topics that I’ve discussed here at Epigenetics News. Many of these e-mailers have made some false assumptions. In light of this, I would like to make a few points very clear to our readers:

  • While I try to summarize news and research articles related to epigenetics, this in no way associates me with the research being conducted. It does not provide with me with additional “inside” information nor can I extrapolate from research to answer questions not addressed in those research articles. No epigenetics research is conducted by Epigenetics News.
  • I am not an expert in epigenetics. I am a student researcher that happens to work in a lab conducting a study related to epigenetics, and this has provided me with a topic of interest to explore and hopefully teach others along the way. So as I attempt to learn more about epigenetics, hopefully my readers will learn more about epigenetics as well.
  • I am not in a position to provide investment advice regarding companies covered at Epigenetics News.

With that said, I fully expect that the majority of my search engine traffic will never see this post and will continue to send me e-mails asking for investment advice and expert opinion. Regardless, I hope that this post may invite readers to at least read through the About page which details who the authors are and a little more information how the information on this site is gathered and dispensed.

Happy Holidays!


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I would like to wish our readers a safe and happy holidays. As for me, this is winter break time at Washington State University, which means that I have just completed my time off from school/work and will now spend the remainder of break in the lab. I am continuing work on a paper as well as keeping up with work on a research project studying the transgenerational effects of endocrine disruptors. The break looks good on paper for getting lots of things done, but in practice the break is over by the time you’ve got the problems worked out of the PCR parameters and the assays are running smoothly.

As for Epigenetics News, expect more research coverage and other items that I’m cooking up for the coming year. I have appreciated the feedback and comments that I’ve received on specific topics that people would like to see more coverage on. Please drop a line in the comments as to your take on the site thus far or what you would like to see done in the coming year. I promise to respond to all as quickly as possible.

Was 2006 a Good Year for Epigenetics?


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Epigenetics, the study of heritable changes not involving changes in DNA sequence, saw a huge boost in public awareness in 2006. There were a number of high profile discoveries in the realm of epigenetics that were unveiled (or progressed) in 2006, which aid in increasing awareness of the field as a legitimate avenue to exciting advancements such as cancer treatment, early screening for cancer, the fetal basis of disease, and epigenetic inheritance in mammals.

  • The Journal of Epigenetics made its debut in 2006, which offers a new venue for topics such as DNA methylation, maternal and paternal imprinting, and histone modifications.
  • Discover Magazine featured a cover story on epigenetics, informing the larger public about the major advances that epigenetics is having on various areas of science and health.
  • Epigenomics, the company developing cancer screening tests based on DNA methylation-based biomarkers, made good progress during 2006, but encountered major setbacks during the latter half of the year. It will be interesting to see how Epigenomics fairs in 2007.
  • A new voice for epigenetics emerged in the form of a blog that aims to cover discoveries and advances in this sparsely covered field.

There were a number of other advances in epigenetics in 2006 that will be discussed in an upcoming post.

Update: Part 2 is now available.

Epigenomics Reviewing Options for Commercialization of Cancer Screening Tests


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Following the recent announcement of the end of the the Roche collaboration, Epigenomics has issued a press release indicating its intent to “review all options for a fast commercialization of the cancer screening tests.”

    Epigenomics AG (Frankfurt, Prime Standard: ECX) today announced that Roche Diagnostics has notified the company about the termination of the joint collaboration focusing on the development of a range of molecular diagnostic cancer products. Roche Diagnostics will return all rights and licenses including the first marker, Septin 9, which it had licensed in December 2005. Roche Diagnostics took the decision after the presentation of new clinical data from the colorectal cancer screening test program.In a prospective study on 561 blood plasma samples, Epigenomics validated that a modified sample processing workflow and a marker panel consisting of Septin 9 and one novel biomarker, improved the detection of early stage (I-III) colorectal cancer with 66% sensitivity and 93% specificity significantly over studies with Septin 9 alone reported in 2005.In another study in its prostate cancer screening program with Roche, Epigenomics detected prostate cancer with a sensitivity of up to 74% at a specificity of 96% using single proprietary DNA methylation biomarkers on urine samples of prostate cancer patients and healthy individuals.Epigenomics is convinced that the quality of the new data allows the further development and commercialization of in vitro diagnostic test products for early detection of cancer. Now that Epigenomics has full control over all its product development programs, the company will review all options for a fast commercialization of the cancer screening tests.

    END OF AD HOC

    “Our new colorectal cancer screening data clearly exceeds expert’s desired performance target for a product that could address this huge market successfully. We are disappointed about Roche’s decision and strongly disagree with their impression that our data does not support a development decision.,” states Christian Piepenbrock, COO of Epigenomics. “We as Epigenomics believe the performance of our colorectal biomarker panel warrants further development and commercialization to make patients benefit as soon as possible from this urgently needed blood test”.

    In September 2002, Epigenomics and Roche entered into a broad collaboration to develop a range of molecular diagnostic cancer products based on Epigenomics’ DNA methylation technologies. The collaboration focused at last on the development of three in vitro diagnostic products for the early detection of colorectal, prostate, and breast cancer.

    Epigenomics in all three programs was responsible for biomarker research including discovery, selection and pre-validation of biomarker panels in clinical proof-of-concept studies. At the end of the research phase, Roche Diagnostics had the right to obtain a world wide exclusive license for the prevalidated biomarker panel and a non-exclusive license to Epigenomics’ DNA methylation technology to develop and commercialize in vitro diagnostic test kits for the biomarker panels in the respective applications. Diagnostic test development, pivotal clinical trials, product manufacturing, regulatory submissions and all sales and marketing worldwide were to be conducted by Roche.

    Under the terms of the agreement, Roche made an upfront payment of EUR 4 million and in addition provided R&D funding, milestone payments and was to provide royalties on product sales. Since 2002, Epigenomics has met a series of major milestones in this collaboration, which was originally earlier this year extended by 18 months to September 2007. Link

Epigenomics Conference Set for March 19-20 in San Diego


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Cambridge Healthtech Institute (CHI) has announced the preliminary agenda for its inaugural epigenetics conference, Epigenomics: Applying DNA Methylation and Histone Acteylation to Diagnostic and Drug Development. The conference will be held March 19-20 at the Hilton San Diego Resort in San Diego, CA. The keynote speaker will be Peter Jones, director of the Norris Comprehensive Cancer Center at the University of Southern California and a leader in the field of epigenetics.The four major topics to be highlighted at the conference:

  • Methylation Profiling
  • Biomarker & Diagostic Development
  • Real-Time Methylation-Specific PCR
  • Epigenetically-Effective Drugs – HDAC & Beyond

Registration is available from now until February 9, 2007 at a reduced price of US$1,195 for commercial attendees or US$620 for academic, government, and hospital-affiliated attendees. Registration includes access to all conference sessions, posters, and exhibits, food functions, and a copy of the conference CD. A poster presentation at the event, with abstracts due by February 9, 2007, entitles the presenter to a $50 discount.

Epigenetics News is a sponsoring publication of this event.

A Student’s Guide to Working in a Research Lab


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I’m now working in my third research lab as an undergraduate student. I wasn’t fired from either of the previous two positions. Rather, I switched positions as better opportunities became available.Many students find it difficult to find employment in a research lab. I didn’t. Here’s a few tips that may help students out there find a job in a research lab on their campus:

  1. Be flexible. If you’re only willing to accept a specific position that will enable you to do something, the odds of you finding a position that satisfies your specific requirements are slim. Further, you’re probably not qualified for that position. Instead, be willing to do the things that other people hate to do. In addition, keep your schedule as open as possible. Everyone knows that you have classes at certain times, but saying that you’re not willing to work before noon due to your sleep schedule will not win you any jobs on campus.
  2. Do your homework. This has nothing to do with your courses, but rather the lab where you’re trying to get a position. Find out about the research that’s being conducted in the lab. Talk to people working in the lab about the research, and what kinds of procedures are done regularly in the lab. Read recent research papers published out of the lab, and visit the principal investigator’s web site (nearly all of them have one) where they detail their research interests. With this information in hand, you’ll come across as knowledgeable and enthusiastic when you tell the person hiring that you’re very interested in this aspect of their research, and tell them in a letter or during an interview that it will be a tremendous experience for you to work in their lab on one of these projects.
  3. Advertise all of your skills. Whether you’re coming in with plenty of lab experience or none at all, you may have a skill that the lab could definitely use, and you may not have thought of it. For instance, you may be very technologically savvy, and have Web design or database management skills. You may have experience with simple lab materials from a high school chemistry or science course. (Almost) anything that allows you to distinguish yourself from the other applicants is a good thing.
  4. Be excited/interested/focused on this lab. Some students make the mistake of thinking that if they make it sound as if they have options, this lab will think that they are in a competition for this student, and they are a high quality hire. This couldn’t be further from the truth. Most lab managers will pass on a student that has options elsewhere. Lab technicians want to spend as little time as possible interviewing students, and saying that you have other options available to you means that you might not accept this position if they offer it. So they just won’t offer it to you, even if you were probably the best candidate.
  5. Follow up. If you were interviewed for a position, come back the next day and drop off a thank you card for the interview, and again express your enthusiasm for working in this position. If there were any “coin-flips” in terms of you or another candidate being selected, this simple gesture will likely give you an edge over another student. The thank-you card is something that few if any other students will take the effort to do, and will help you distinguish yourself as the lab is preparing to select their best candidate.

Special Offers Worth Mentioning


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I noticed that SEED Magazine, which now hosts 52 great science blogs, will be featuring these blogs in a special issue of the magazine, The Year in Science 2006. You can get this special issue plus a year’s subscription (6 issues) for US$14.95. A cartoon picture of Seed’s bloggers will be featured in the special issue and can be previewed here.

In addition, How to Change the World notes that Jajah will be offering free global phone service on Christmas Day. This will allow a registered Jajah user (registration is cost and obligation free) to set up a conference call between 10 family members, for instance. The list of 80 countries in which calls can be placed are available here. (I figured this one may be useful for all of the visiting scientists with families in their countries of origin.)

Roche Terminates Cancer Screening Collaboration with Epigenomics


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Roche Diagnostics has announced that it has decided to end its 4-year collaboration with Epigenomics (ECX GY). The entire statement follows:

    Roche Diagnostics announced today that it has decided to terminate its 4-year collaboration with Epigenomics to develop prostate, breast, and colorectal cancer screening diagnostic tests based on Epigenomics’ DNA methylation technologies. Roche determined that the colorectal cancer screening data presented by Epigenomics to date did not meet Roche criteria for development as in vitro diagnostic tests.
This announcement will most likely be followed by a press release from Epigenomics inidicating that they are in the process of seeking a new partner to develop cancer screening diagnostic tests based on their methylation technologies. However, this news follows an October 26 announcement that the company would focus its efforts on late-stage product development, and lay off approximately one-third of its Berlin staff. The end of the Roche collaboration may be too much for the company to overcome.

Update: Epigenomics stock has fallen following the announcement of the end of the Roche collaboration. MarketWatch also has comments from Epigenomics CFO Oliver Schacht on their “ongoing discussions” with diagnostic partners for licensing the rights to the diagnostic tests.

Epigenetics in X-Linked Mental Retardation


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New research, currently in press from the international Journal of Cellular and Molecular Medicine, describes (speculative) evidence for an epigenetic link to human mental retardation.

    The search for the genetic defects in constitutional diseases has so far been restricted to direct methods for the identification of genetic mutations in the patients’ genome. Traditional methods such as karyotyping, FISH, mutation screening, positional cloning and CGH, have been complemented with newer methods including array-CGH and PCR-based approaches (MLPA, qPCR). These methods have revealed a high number of genetic or genomic aberrations that result in an altered expression or reduced functional activity of key proteins. For a significant percentage of patients with congenital disease however, the underlying cause has not been resolved strongly suggesting that yet other mechanisms could play important roles in their etiology. Alterations of the ‘native’ epigenetic imprint might constitute such a novel mechanism. Epigenetics, heritable changes that do not rely on the nucleotide sequence, has already been shown to play a determining role in embryonic development, X-inactivation, and cell differentiation in mammals. Recent progress in the development of techniques to study these processes on full genome scale has stimulated researchers to investigate the role of epigenetic modifications in cancer as well as in constitutional diseases. We will focus on mental impairment because of the growing evidence for the contribution of epigenetics in memory formation and cognition. Disturbance of the epigenetic profile due to direct alterations at genomic regions, or failure of the epigenetic machinery due to genetic mutations in one of its components, has been demonstrated in cognitive derangements in a number of neurological disorders now. It is therefore tempting to speculate that the cognitive deficit in a significant percentage of patients with unexplained mental retardation results from epigenetic modifications.
Link

I Never Knew Writing (Research) Could Be So…


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Laborious. Frustrating. Infuriating. Foreign.

Tonight I came across some comments from Derek Lowe, a chemist who writes great commentary on the pharmaceutical industry and a number of other topics in science at In the Pipeline, on the importance of “brevity” in describing research.

    Some of the worst writing in the scientific journals, though, comes from people who are trying to turn out the best. I’ve seen several people who are overly impressed with their writing skills, and try to dress up their papers with knotty sentence structure, recondite vocabularly, and other cheap tricks. Unfortunately, many readers fall for it. If they can recognize the author’s style, they figure, he must be some writer. A journal article doesn’t give you much room for style, that’s for sure. Having an individual voice for your publications is a real challenge, but here’s the trouble: most of the ways you can do it are bad ideas.
I couldn’t pass up this opportunity to discuss my own thoughts on the writing of research, as someone who comes from a background in writing for the Web.

As some of you know, I’m currently in the process of writing my first research paper. This follows on the heels of a number of other firsts: first time that I’d been involved in a research project, first time that I’ve presented research during a poster session at a conference, first time that I took a course in genetics. But I thought I had a decent handle on writing. After all, I had done a fair bit of writing as an editor and writer prior to returning to college to pursue a career in science.

Well, as it turns out, writing a research paper isn’t anything like the writing I’m accustomed to.

This should have been very apparent to me, because I’ve now read and been introduced to hundreds of research articles in a number of different disciplines. But it didn’t really hit me until I got some of my first edits back from my lab mentor.

As it turns out, smooth transitions between topics are out; short, simplistic statements of data (the good stuff) is in. I have never written something so lifeless and cold. I’ve been asked to take my experience in writing things that “everyday” people want to read, and turn that into writing something that scientists would have to read: hard data. No frills, no gimmicks.

It’s been a laborious process, because it seems that with every little change, it begins a cascade in which a number of other areas of the paper must be edited to reflect it. I’m sure that this comes as no surprise to those of you with publication lists in the dozens or hundreds of lines, but to a newbie like myself, this is weird stuff.

And frustrating? I have no doubt that I haven’t even begun to feel real frustration, but I’m on the leading edge of what could be the most frustrating writing experience that I’ve ever had.

The biggest surprise to me in undertaking the writing of this research paper is how foreign the process is, even to a writer and editor like myself. I’m sure every PI has their own system of leading a graduate student, postdoc, etc. in the construction of a research paper, but the process that I’ve encountered thus far is so beyond recognizable as anything that I would call “editing” or “writing.” I would describe it more as “fixing something for the sake of probability to publish,” or, perhaps more appropriately, “incoherent nonsense to layman, perfectly sensible strategy to scientist.”

BioServe Unveils DNA Methylation Analysis Service


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Laurel, MD-based BioServe Biotechnologies has unveiled a new service to analyze the ratio of methylation within a specific region of genomic DNA. The service utilizes Sequenom’s MassARRAY System and EpiTYPER methodology.

    DNA methylation markers are a new and important class of biomarkers that are significant because of their correlation to gene activity. High levels of cytosine methylation in genomic regions (CpG islands) are often associated with decreased or completely inhibited gene expression. Researchers now believe that DNA methylation patterns play an important role in early cancer detection and prognosis. BioServe’s Methylation Analysis Service will aid researchers’ understanding of methylation patterns with quantitative results in the form of methylation ratios in targeted genomic regions.

Link

Imprinting Finding May Aid in Colorectal Cancer Screening


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Dr. Andrew Feinberg of the John Hopkins School of Medicine has announced at the 46th Annual Meeting of The American Society for Cell Biology that his lab has analyzed a common epigenetic alteration and found that mice with the loss of imprinting of IGF2 and a mutation in the Apc gene have a higher risk of developing colon cancer.

    Feinberg analyzed a common epigenetic alteration—found in 5–10 percent of the general population—that involves the loss of imprinting on an insulin-like growth factor gene called IGF2. Loss of imprinting of IGF2 has been associated statistically with individuals who have personal and familial histories of colorectal cancer. Turning to mice that modeled the loss of IGF2 imprinting, Feinberg found an increase in frequency of tumors in mice who also had mutations in a cancer-associated gene called Apc. In the mutant Apc mice, the loss of IGF2 imprinting seems to particularly affect the behavior of the adult stem cells that continually regenerate the colon in mice. This probably plays a role in the increased risk of colon cancer, says Feinberg.

This finding may help to develop better colon cancer screening tools. Link

Harvard Epidemiologist Seeks Postdoc in Epigenetics


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Dr. Karin Michels, an associate professor of Harvard Medical School and clinical epidemiologist of Brigham and Women’s Hospital, is seeking a postdoctoral research associate for her lab in Boston, MA.

    A postdoctoral position will be available at Brigham and Women’s Hospital, Harvard Medical School, to study gene imprinting and methylation starting in February or March 2007. The focus of our research is to identify environmental factors that predict loss of imprinting. A birth cohort is available to study epigenetic variation in newborns. We also examine imprinting pattern in human breast cancer. Candidates with strong background in molecular biology and epigenetics are encouraged to apply. Experience in human genome research and transcriptional gene regulation is particularly desirable.
Dr. Michels’ research interests focus on nutrition and women’s health (via Harvard School of Public Health):
    Her research ranges from early intrauterine nutrition of the fetus, breastfeeding and early life and adolescent diet to the role of adult diet on chronic disease risk, in particular, breast and other cancers. As diet is difficult to assess, Dr. Michels is studying the degree of measurement error associated with the different diet assessment methods. She is developing improved methods to analyze dietary data in epidemiologic studies. Dr. Michels is the Principal Investigator of a research grant from the National Institutes of Health to explore methods in nutritional epidemiology in the Nurses’ Health Study.

    Dr. Michels is also exploring the role of intrauterine and early life exposures in chronic diseases in adult life. Numerous studies have indicated that events in vitro may affect the risk of chronic disease in the offspring later in life. Dr. Michels is using several databases around the world to study this challenging hypothesis in more detail.

Dr. Karin Michels’ most recent publications. Link