A former hepatitis virus researcher reminisces on the progress made and challenges remaining in the fight to eradicate chronic viral hepatitis.

World Health Alliance World Hepatitis Day 2014 Campaign Poster

July 28, 2014.  “Hepatitis: Think Again.”  That is the motto for this year’s World Hepatitis Day, a program championed by the World Hepatitis Alliance to raise awareness, encourage prevention, and improve access to treatment for viral hepatitis.  The World Health Organization (WHO) endorsed the global recognition of this event in 2010.  Chronic viral hepatitis has been called a “silent killer” since often no symptoms are apparent until a life-threatening condition develops.

Hepatitis refers to liver inflammation, which is frequently caused by infection with a number of unrelated liver viruses 

Hepatitis refers to liver inflammation, which is frequently caused by infection with a number of unrelated liver viruses termed hepatitis viruses A-E.  The hepatitis viruses A (HAV) and E (HEV) are generally self-limiting causes of food poisoning, while infection with the blood-borne hepatitis B (HBV) or C viruses (HCV) can lead to chronic hepatitis, which may cause long-term cirrhotic damage, end-stage liver disease, and hepatocellular carcinoma (HCC).  Hepatitis D (HDV) exacerbates HBV infections.  It is only observed in HBV-infected individuals, and not in isolation, since it requires the HBV coat protein to replicate.

Hepatitis B

About a third of the people on the planet have been infected with HBV at one time or another and there are an estimated 360 million people chronically infected with hepatitis B (WHO Weekly epidemiological record). This highly-infectious DNA virus is easily spread from blood, blood products or sexual intercourse, but not from causal contact, like hugging or kissing. Routine serological testing has screened it out of blood since the late 60s.  In highly endemic regions, such as China, the virus is predominantly spread perinatally, whereas in the developed world, anti-HBV immunoglobulin (HBIG) treatment is routinely used to block that transmission, followed by vaccination of the newborns.  Most of the new hepatitis B cases seen in the US and in other developed nations can be traced to preexisting infections in immigrants from Asia, the Pacific Islands, and from several other low-moderate income countries (CDC Viral Hepatitis Facts).

A blood-derived HBV vaccine was being used by the late 70s; while the recombinant DNA-based version of this vaccine widely-used today was introduced in the 80s.  This vaccine is amongst the most widely-used, efficacious, and safest products that biotechnology has created.  HBV infection is the major cause of HCC development, so this vaccine is also considered the first anti-cancer vaccine.  Approximately one third of newborns worldwide are being vaccinated against HBV today and this appears to generate life-long immunity against the virus (WHO Weekly epidemiological record).  Numerous long-term clinical studies have found no evidence of any serious adverse event or disease association linked to the use of this vaccine (WHO Weekly epidemiological record).

Nucleosides are the mainstay of HBV therapy and the latest versions of these molecules are generally well-tolerated and quite effective at completely suppressing the virus.  Yes, rare exceptions due to viral mutations and other underlying comorbid and psychosociological conditions do complicate this.  And, in addition, the hardy nature of the HBV covalently-closed circular (cccDNA) genome necessitates long-term use of these drugs to keep the virus suppressed, but HBV antivirals generally work well.

Hepatitis C

Virtually all of the non-A, non-B post-transfusion hepatitis described years ago in textbooks were found to be attributable to HCV after its RNA genome was cloned in the late 80s.  It is estimated that there are 180 million people chronically-infected with HCV.  Detection is routine and the virus is therefore largely screened out of the world’s blood supply.  But individuals who have received blood or blood products before this time may have inadvertently contracted HCV.  HCV is less transmissible than HBV and usually involves direct injection of blood or blood-products into the bloodstream and monogamous heterosexual couples have a low risk of contracting it from an infected mate (CDC Hepatitis C Information for Health Professionals).  Most of the HCV transmission today in the developed world is among intravenous drug users, while those who experimented even only once with injectable drugs are at risk of being infected (CDC Viral Hepatitis Statistics & Surveillance).

There is no vaccine for HCV and there is no expectation that an effective vaccine will be available anytime soon.

While HCV has caused a lot of hurt and suffering in the world, it turns out that the virus itself is a wimp. In fact, HCV infection is the only chronic viral infection that can be cured using antiviral agents.  Every few years a new generation of HCV antivirals emerges with better cure rates— but at a greater expense. The latest treatment regimens using Direct Acting Antivirals claim 90% cure rates— and a near $100,000 treatment pricetag ($1,000 per pill).  The WHO guidelines and recommendations for healthcare providers in low- to middle-income countries regarding hepatitis C released this year addresses the challenges faced in the management of this disease with limited economic resources.

Summary

Tremendous strides have been made in the past generation to identify, prevent and cure chronic viral hepatitis, but with over half a billion people infected with HBV and HCV worldwide, it remains a major public health issue—the biggest problem continues to be that most people don’t know that they are infected. The motto for this year’s World Hepatitis Day reemphasizes how critical it is for anyone with a risk factor for HBV or HCV infection to be tested because the battle against viral hepatitis is being won, but the war is not over.

The Radiant Creations Group, Inc. (RCGP) Announces Nucleotide Technologies "Spinoff"

PALM BEACH GARDENS, FL--(Marketwired - July 28, 2014) - The Radiant Creations Group, Inc. ("Radiant") (OTCQB: RCGP), developer of unique, proprietary scientific technologies and cosmetic and over-the-counter products and devices, is pleased to announce at its regularly scheduled Board meeting held on July 3, 2014 the Directors agreed to "spinoff" the Company's exclusive license agreement with Dr. Yin-Xiong Li, MD, Ph.D. The new Company name will be NIT Enterprises, Inc. (Nucleotide Industrial Technologies). The Exclusive license agreement includes patented and patent-pending technologies for the development of innovative nucleotide technologies or nucleic acid (NA) code molecules, applications for the technologies to be directed at industrial facilities, medical facilities, hospitals, the welding industry and military and homeland security markets.

Nucleotides are any of a group of molecules that, when linked together, form the building blocks of DNA or RNA: composed of a phosphate group, the bases adenine, cytosine, guanine, and thymine, and a pentose sugar. ("http://dictionary.reference.com/browse/nucleotide")

After a decade and a half of intense genetic research by Dr. Yin-Xiong Li, MD, Ph.D., the true capability of nucleic acid code molecules were discovered and brought to a commercially exploitable state through one granted patent and one applied patent, to be exclusively licensed to NIT.

Gary Smith, CEO, Radiant, stated, "This discovery ranks as one of the most profound and valuable discoveries for almost limitless technological enhancement in industrial, medical and the chemical development. The potential revenues to be generated by commercialization of these exclusive NA technologies can be exploited through manufacturing NA as a raw material, and licensing production for a myriad of applications which are also expected to generate significantly more intellectual property enhancements."

Radiant's exclusive license included documentation that concluded, NA free of the DNA ladder has been shown to protect against the harmful effects of Ultraviolet light (UV) radiation across a wide band of UV spectrum. NA performs its unique function when it is free to react with photons and UV rays. When a damaging UV photon hits a freed NA molecule, it is absorbed and then re-emitted as a harmless infrared (heat) photon into the atmosphere. The NA may remain undamaged and continues to perform its protective function.

Proposed applications and future testing to include identifying methods to enhance protection from ionizing radiation such as X-Rays and Gamma Rays providing NIT with effective solutions to reduce the impact of radiation, thus creating a market for protecting government and institutional public buildings, hospitals, clinics, dentist and doctor's offices and industrial facilities; anywhere there is use of ionizing radiation.

Shareholders of record of The Radiant Creations Group, Inc. (RCGP) will receive (proportionally) shares of NIT Enterprises, Inc. following the completion and effectiveness of the required SEC filings. The Company will announce the Record date for the issuance of "spinoff" shares upon completion of required legal compliance.

About The Radiant Creations Group, Inc. (RCGP) (www.radiantcreations-rcgp.com)

Radiant Creations has achieved exciting breakthroughs creating remarkable products in skin protection and hydration, anti-aging, liver health and weight balance by combining DNA derived technologies developed in the Western World and naturally acting traditional Chinese medicine ingredients believed never before used in western culture by any bioscience company.

Among these exciting discoveries is a new and superior mechanism of defense against skin deterioration and damage caused by sun exposure to ultraviolet (UV) light using the nucleotides, four "code molecules" extracted from DNA. This revolutionary mechanism also has great significance and value in many other cosmetic and non-cosmetic applications requiring UV protection, and is among Radiant Creations' licensed intellectual property. The technology will be implemented across numerous innovative product lines.

About NIT Enterprises, Inc. (NIT) (www.NITEnterprises.com)

NIT Enterprises, Inc. (d/b/a Nucleotide Industrial Technologies) (NIT) was created to improve public safety and to provide a new measure of protection for commercial, industrial, and personal products that enhance the longevity of living and non-living substances based upon unique proprietary NA technologies developed by our award winning scientist and technology team. This new technology is the infusion of ingredients, known as nucleotides, into a multiplicity of common products enhanced by their presence. The Nucleotides were derived by atomic level research that demonstrates their ability to provide Ultraviolet (UV) rays screening capability at the molecular level.

Cautionary Statement Concerning forward-Looking Statements:

This press release contains forward-looking statements that can be identified by words such as "anticipates," "intends," "plans," "seeks," "believes," "estimates," "expects" and similar references to future periods.

Forward-looking statements are based on our current expectations and assumptions regarding our business, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Our actual results may differ materially from those contemplated by the forward-looking statements. We caution you therefore against relying on any of these forward-looking statements. They are neither statements of historical fact nor guarantees or assurances of future performance. Any forward-looking statement made by us in this press release speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law.

Corporate Contact Information:

The Radiant Creations Group, Inc.

Harbour Financial Center

2401 PGA Boulevard, Suite 280-N

Palm Beach Gardens, FL 33410

Phone: 561-283-4740

Investor Relations:

Gary D. Alexander

Corporate Secretary

Email: G.Alexander@RadiantCreationsGroup.com

Forced mutations doom HIV

CAMBRIDGE, MA -- Fifteen years ago, MIT professor John Essigmann and colleagues from the University of Washington had a novel idea for an HIV drug. They thought if they could induce the virus to mutate uncontrollably, they could force it to weaken and eventually die out — a strategy that our immune system uses against many viruses.
The researchers developed such a drug, which caused HIV to mutate at an enhanced rate, as expected. But it did not eliminate the virus from patients in a small clinical trial reported in 2011. In a new study, however, Essigmann and colleagues have determined the mechanism behind the drug's action, which they believe could help them develop better versions that would destroy the virus more quickly.
This type of drug could, they say, help combat the residual virus that remains in the T cells of patients whose disease has been brought into long-term remission by the triple-drug combination typically used to treat HIV. These viruses re-emerge periodically, which is why patients must stay on the drug cocktail indefinitely and are not considered "cured."
"This has really been the biggest problem in HIV," says Essigmann, the William R. and Betsy P. Leitch Professor of Chemistry, Toxicology, and Biological Engineering at MIT. "What we would hope is that over a long period of time on this type of therapy, a person would potentially have their latent pool mutated to the extent that it no longer causes active disease."
In the new study, which appears in the Proceedings of the National Academy of Sciences (PNAS) the week of July 28, the researchers discovered exactly how the drug, known as KP1212, induces the HIV genome to mutate. The paper's lead authors are MIT postdocs Deyu Li, Bogdan Fedeles, and Vipender Singh, along with recent MIT PhD graduate Chunte Sam Peng. Essigmann and Andrei Tokmakoff, a former MIT professor who is now at the University of Chicago, are the paper's senior authors.

Too much mutation

After HIV infects a cell, it rapidly begins making copies of its genetic material. This copying is very error-prone, so the virus mutates swiftly. This usually helps the virus survive by allowing it to evade both the immune system and human-made drugs. However, at a conference in the late 1990s, Essigmann learned from an evolutionary biologist that if the virus could be forced to double its mutation rate, it would no longer be able to produce functional proteins.
Essigmann and Lawrence Loeb, a professor of biochemistry at the University of Washington, started working together to exploit this idea. Essigmann had been developing compounds that mimic natural nucleotides — the A, C, T, and G "letters" that form DNA base pairs — but that induce genetic mutations by binding with the wrong partner. Loeb is an expert on polymerases, the enzymes that string nucleotides together to form DNA or RNA.
Together with James Mullins, an immunology professor and HIV expert at the University of Washington, Essigmann and Loeb designed a molecule called 5-hydroxycytosine, described in a 1999 PNAS paper. When given to HIV-infected cells grown in the lab, this molecule was incorporated into the viral genome in place of the natural form of cytosine. Within 25 viral replication cycles, HIV populations in those infected cells collapsed.
The researchers then formed a company, Koronis Pharmaceuticals, which developed KP1212, a compound that is 100 times more mutagenic than 5-hydroxycytosine. In a four-month clinical trial of 32 patients, mutations accumulated in the patients' viral DNA, but not enough to induce a population crash. The drug was also found to be safe: It did not mutate the patients' own DNA, in part because the drug was designed so that human forms of DNA polymerase could not accept it.

Shape-shifting molecules

In the new PNAS paper, the researchers used advanced spectroscopy techniques to analyze KP1212's ability to promote tautomerism, a chemical phenomenon that involves the migration of protons among the nitrogen and oxygen atoms on nucleic-acid bases. This allowed the researchers to see that once KP1212 inserts itself into the genome, it can switch among five different shapes, or tautomers. Some of these behave like cytosine, by pairing with guanine. However, some of the tautomers resemble thymine, so they will pair with adenine, introducing mutations.
"The five molecules are changing shape on a nanosecond timescale, and each shape has a different base-pairing property, so you will see a promiscuity in terms of the bases with which KP1212 pairs," Singh says.
To see this shape-shifting, the researchers used NMR and a form of 2-D infrared spectroscopy developed by Tokmakoff. This technology allows scientists to determine the atomic composition and structure of nucleic-acid bases.
Then, using a genetic tool developed in the Essigmann lab, the researchers determined that KP1212 induces a mutation rate of exactly 10 percent in the HIV genome. Based on these findings, Essigmann estimates that if KP1212 doubles the mutation rate of HIV, it could clear the virus from patients in one to two years.
He says that Koronis hopes to run a longer trial of KP1212 and is also interested in developing drugs that would work faster, which could be accomplished by altering some of the chemical features of the molecule and testing whether they speed up the mutation rate.
The paper also identified other factors that scientists could manipulate to improve the drug's performance.
"There are other variables that are important to calculate the time it would take to eradicate a virus," Fedeles says. "That includes the concentration that the drug needs to achieve inside the cell, and the ability of a cell to convert the nucleoside, the molecule without the phosphate, to the triphosphate version, which is the one incorporated by the polymerase."
"We're building up a new strategy that can give us a lot of insights into how to design a new molecule," Li says. "It's a new toolset for developing future drugs. Those drugs are not limited to HIV. They could be candidates for dengue fever, or some other viruses such as yellow fever."
Ribavirin, a drug used to treat hepatitis C, and the influenza drug T-705 are also believed to provoke hypermutation in their target viruses. The MIT team also plans to work with Loeb to test the possibility of using similar compounds to force tumor cells to mutate themselves into extinction.

Source: Massachusetts Institute of Technology

HIV virus removed from cells for first time

A team of researchers at Temple University for the first time developed a way to extract HIV from human cells in a lab setting. (Public domain image of a scanning electron micrograph of HIV-1 budding, in green, from cultured lymphocyte by the CDC/C. Goldsmith, P. Feorino, E.L. Palmer and W.R. McManus)

A team of researchers at Temple University in Philadelphia for the first time developed a way to extract the HIV virus from human cells in a laboratory setting, opening the way for further studies that could lead to a cure for AIDS.

In a study published July 21 in the journal Proceedings of the National Academy of Sciences, researchers said they developed a “DNA-snipping enzyme” called nuclease and a strand of RNA capable of targeting and removing the DNA of the HIV-1 virus from human cells.

“From there, the cell’s gene repair machinery takes over, soldering the loose ends of the genome back together – resulting in virus-free cells,” according to a statement released by the Temple University School of Medicine. A genome refers to the genetic material in cells.

- See more at: http://www.washingtonblade.com/2014/07/28/hiv-virus-removed-cells-first-time/#sthash.Wk634zOt.dpuf


“This is one important step on the path toward a permanent cure for AIDS,” said Kamel Khalili, professor and chair of the Department of Neuroscience at Temple and the lead researcher in the HIV “removal” finding. “It’s an exciting discovery, but it’s not yet ready to go into the clinic,” Khalili said in the statement released by the Temple medical school. “It’s proof of a concept that we’re moving in the right direction.” Khalili, who heads a team of researchers that worked on the study, noted that since the human immune system cannot now remove HIV-1, a means of removing the virus through medical intervention is needed to find a cure for AIDS. His research team found that the technique they developed to extract HIV-1 from cells might also work as a “therapeutic vaccine.” Cells treated with the nuclease-RNA combination they developed “proved impervious to HIV infection,” the Temple statement says. The statement points out that although anti-retroviral drugs are highly effective in controlling HIV-1 for infected people, the virus remains hidden in the body’s cells and can replicate in large numbers and cause serious health consequences if treatment is interrupted. While promising, the new technique to remove HIV-1 from human cells faces a number of challenges before the technique is ready for patients, Khalili said in the statement. Among other things, he said researchers must develop a method to deliver the therapeutic agent to every infected cell as well as a means to countering the ability of HIV to mutate. “We are working on a number of strategies so we can take the construct into preclinical studies,” he said. “We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it. - See more at: http://www.washingtonblade.com/2014/07/28/hiv-virus-removed-cells-first-time/#sthash.Wk634zOt.dpuf

Stress-tolerant tomato relative sequenced

Wild tomato species are not edible, but they can be bred with domestic tomatoes to introduce new traits such as flavor and drought resistance. A new genome sequence for wild...

The genome of Solanum pennellii, a wild relative of the domestic tomato, has been published by an international group of researchers including the labs headed by Professors Neelima Sinha and Julin Maloof at the UC Davis Department of Plant Biology. The new genome information may help breeders produce tastier, more stress-tolerant tomatoes.

The work, published July 27 in the journalNature Genetics, was lead by Björn Usadel and colleagues at Aachen University in Germany. The UC Davis labs carried out work on the transcriptome of S. pennellii — the RNA molecules that are transcribed from DNA and then translated into proteins — messages written from DNA and taken to other parts of the cell to tell it what to do. Analyzing the RNA transcriptome shows which genes are active under different circumstances. The UC Davis team published a paper last year comparing the RNA transcripts of domestic tomato and three wild relatives, including S. pennellii.

S. pennellii is inedible, but it can be interbred with domestic tomatoes to introduce useful traits, such as drought resistance. Using the new genome data, the researchers found genes related to dehydration resistance, fruit development and fruit ripening. They also found genes that contribute to volatile compounds related to fruit scent and flavor.

Gene research targets scarring process

One is known to promote collagen (what scars are made of) production in the gut and another in the tendons, while the third aids tissue development in the hands, arms and heart.iStock

SCIENTISTS have identified three genes that may be the key to preventing scar formation after burn injury, and even healing existing scars.

In a world-first study, researchers at UWA's Burn Injury Research Unit found changes in the DNA and RNA of scarred skin cells compared to healthy ones.

They say treatments targeted at these genes could reverse the process that leads to scars being retained as the body makes new cells over its lifespan.

The researchers compared samples from burnt forearms of six patients to samples from the same sites on their undamaged arms with methylation and gene arrays to look for epigenetic changes—inheritable changes to the DNA other than to the DNA sequence itself.

Tissue is built when proteins bind to DNA and get a blueprint in the form of RNA that tells cells to build skin, hair, bone or muscle in a certain way.

Methylation is where methyl groups are added to the DNA at specific sites, stopping them being read by the proteins.

The researchers found burn injury changes this process, causing lasting effects to the tissue created.

Methylation analysis of the DNA identified 3298 methylation sites (out of 485,000) on 398 genes to have altered methylation patterns compared to the controls.

Gene expression analysis of the RNA showed 113 genes that were turned on or off differently to controls.

Scientists hone in on controller genes

Lead researcher, PhD student Andrew Stevenson, says the 113 RNA and 398 DNA altered genes had 14 genes in common and the team chose three for further study that they believe are most involved in the process and most promising for treatment.

"These controller genes are sent off to be made again and again in a positive feedback loop, so small changes can have big effects downstream and can also activate other genes," he says.

One is known to promote collagen (what scars are made of) production in the gut and another in the tendons, while the third aids tissue development in the hands, arms and heart.

"Our techniques right now are quite crude, cutting out scars and shooting lasers into the tissue to make it heal faster and minimise scarring, so this could have big implications for future care," Mr Stevenson says.

"No one has looked at scar tissue at a genetic level before and we are using equipment and tests that have only been around about five years and mostly used to study cancer."

The Cancer Genome Atlas researchers identify

The Cancer Genome Atlas (TCGA) Network researchers have found that stomach cancers fall into four distinct molecular subtypes. In the study, published online July 23, 2014, in Nature, the scientists report that this discovery could change how researchers think about developing treatments for stomach cancer, also called gastric cancers or gastric adenocarcinomas.

Instead of considering gastric cancer as a single disease, as has been done in the past, researchers will now be able to explore therapies in defined sets of patients whose tumours have specific genomic abnormalities. Stomach cancers are a leading cause of cancer-related mortality worldwide, resulting in an estimated 723,000 deaths annually.

Previous attempts to examine the clinical characteristics of gastric cancer were hindered by how differently cancer cells can look under a microscope, even when from the same tumour. The researchers hope that the new classification system will serve as a valuable adjunct to the current pathology classification system, which has two categories: diffuse and intestinal.

“A key advance with this project is that we have identified and developed a much more useful classification system to find groups of gastric cancer that have distinct molecular features, and at the same time, we also identified key targets to pursue in different groups of patients,” said Adam Bass, M.D., Harvard Medical School, Dana-Farber Cancer Institute, the Broad Institute, Boston, and one of the lead investigators on the project. “This will provide a strong foundation for categorising the disease and for doing so in a way in which we can develop clinical trials based on some of the critical molecular alterations that are driving different classes of cancers.”

The researchers identified the new subgroups through complex statistical analyses of molecular data from 295 tumours. They used six molecular analysis platforms including DNA sequencing, RNA sequencing, and protein arrays.

tumours in the first group, which represented 9 per cent of the tumours, were positive for Epstein-Barr virus (EBV) and had several other molecular commonalities. tumours in a second subgroup (22 percent of the tumours) had high microsatellite instability (MSI), which is the tendency for mutations to accumulate in repeated sequences of DNA. The remaining subgroups differed in the level of somatic copy number alterations (SCNAs), which can result from duplication or deletion of sections of the genome. The tumours in the third subgroup, which comprised 20 per cent of the tumours, were considered to have a low level of SCNAs and were called genomically stable. The remaining 50 per cent of tumours were classified as chromosomally unstable, with a high level of SCNAs.

The EBV-positive subgroup of tumours was of particular interest. EBV is best known in the United States as the cause of infectious mononucleosis, which is characterised by fever, sore throat, and swollen lymph glands, especially in the neck. EBV is also suspected of causing certain cancers, including nasopharyngeal carcinoma and some types of lymphoma. Previous research had shown that EBV can be detected in a minority of gastric adenocarcinomas and that EBV genes are expressed in those tumours. However, this study found that the presence of EBV in gastric tumours is associated with a number of other molecular characteristics.

First, the researchers observed that EBV-positive tumours displayed a high frequency of mutations in the PIK3CA gene, which codes for a component of a protein, PI3-kinase, which is essential for cell growth and division and many other cellular activities that are important in cancer. Although 80 per cent of EBV-positive tumours harbored a protein-changing alteration in PIK3CA, PIK3CA mutations were found in 3 percent to 42 per cent of tumours of the other gastric cancer subtypes. The scientists suggested that EBV-positive tumours might respond to PI3-kinase inhibitors, some of which are in the early stages of testing in clinical trials but are not yet approved by the US Food and Drug Administration for general use.

Some tumours in the EBV-positive subgroup also showed more gene copies being produced in a chromosomal region that contains the JAK2 gene. The JAK2 protein facilitates cell growth and division, and the increased expression of JAK2 may inappropriately activate cell growth. The amplified region also contains the genes for two proteins, PD-L1 and PD-L2, which suppress immune responses; their increased expression may help tumours escape destruction by the immune system. The investigators suggested that these findings support the evaluation of JAK2 inhibitors and PD-L1/2 antagonists for the treatment of EBV-positive gastric cancers.

And the EBV-positive subgroup showed a far higher prevalence of DNA hypermethylation than any other cancer subtype reported by TCGA researchers. Methylation is the process of adding methyl groups to DNA, which reduces gene expression. Hypermethylation occurs when this mechanism continues aberrantly, quieting genes that should be active. In the EBV-positive tumour subgroup, hypermethylation was most often observed in the promoter regions of genes, which would prevent the expression of the genes.

"Gaining these insights into the connection between EBV and gastric cancer is the type of groundbreaking research that NIH is pleased to be a part of. We look forward to the potential clinical implications of this discovery," said NIH Director Francis S. Collins, M.D., Ph.D. “This study reinforces the value of the approach we are using to study genomic diversity and similarity among tumours of many different cancer types,” said NCI Director Harold Varmus, M.D. “Only such a systematic analysis could have yielded observations about the association between EBV and several provocative molecular characteristics.”

Important insights also came from analyses of the three other gastric cancer subgroups. For example, tumours of the genomically stable subtype contained frequent mutations in a gene called RHOA, whose product interacts with other cellular proteins to help cells change shape and migrate, which may be important in tumour growth. This finding suggests possible targets for treating tumours of this subtype. And tumours of the chromosomal unstable subtype contained frequent amplifications of genes that encode receptor proteins on the outside of the cell, leading to the promotion of aberrant cell growth. Drugs are already available to curb the activity of some of these proteins.

“This most recent TCGA study again demonstrates the importance of its comprehensive design,” said NHGRI Director Eric Green, M.D., Ph.D. “These results give us important new genomic insights into a cause of a deadly form of cancer."