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16 May 2008A new international collaboration, the International Cancer Genome Consortium, has been launched with the aim of coordinating efforts to catalogue the genomic changes in about 50 different cancer types and subtypes (see press release). It is hoped that this information will lead to new approaches to the diagnosis, treatment and prevention of cancer.
Each member of the consortium will take responsibility for at least one type or subtype of cancer, analysing tumour specimens from about 500 patients. The project is expected to take up to 10 years. The role of the ICGC is to draw up an agreed list of cancers for study, to develop common standards for data collection and ethical oversight, and to facilitate information exchange among consortium members to avoid duplication of effort. Cancer types will be chosen for study on the basis of their impact on morbidity and mortality, the availability of therapies, and the feasibility of collecting sufficient high-quality tumour samples. Participating organisations must meet standards of comprehensiveness (detecting all cancer-related genomic changes occurring in at least 3% of tumour samples), resolution (analysis to the level of individual DNA base changes) quality (adhering to common standards of pathology and technology), and controls (comparisons with matched, non-tumour tissue).
All data will be made freely available to qualified researchers, and ICGC members must pledge not to patent or make other intellectual property claims on any of their primary data. The policies and guidelines developed so far are available from the consortium’s website.
Current ICGC membership includes research organisations from Canada, China, France, India, Japan, Singapore, the UK and the US, while the European Commission and Australia’s National Health and Medical Reserach Council have observer status. All research organisations that accept the policies and guidelines of the ICGC are invited to join the consortium. Funding Members pledge to provide at least $20 million over 5 years to fund a project. Research Members must be nominated by Funding Members that have agreed to provide financial support for their participation.
13 May 2008On 30 April 2008, the UK Human Tissue Authority (HTA) announced the release of regulations that will, for the first time, govern the collection of umbilical cord blood at birth. As stem cells present in cord blood can potentially be used to treat serious diseases such as leukaemia, there is an increasing trend among parents to collect and store the blood for use in the event that the child requires future medical treatment. Various companies will store the blood in a cord blood bank, which acts as an ‘insurance policy’ by securing a source of stem cells that is tissue-matched to the child (see previous news). The practice has raised some concerns, including the potential for commercial exploitation of parents in light of the very low risk that future disease will actually transpire. Commercial services might also divert efforts away from public sector banks such as the NHS Cord Blood Bank.
The new rules, which will take effect from 5th July 2008, emanate from the European Union Tissue and Cells Directive, which was implemented in the UK on 5 July 2007 by the Regulations on Human Tissue (Quality and Safety for Human Application) under the Human Tissue Act. The rules are intended to ensure safety and traceability by requiring that only specially trained individuals may harvest the cord blood, using approved procedures, in hospital maternity units that meet essential standards. An HTA license will require the unit to demonstrate not only that cord blood will be harvested in the proper manner, by qualified staff, but also that procedures are in place to prevent medical attention being drawn away from mother or child during the collection (see BBC news). HTA Chief Executive Adrian McNeil commented: “We are introducing this regulation to make sure that the best quality samples are taken in the safest way…The Human Tissue Authority is one of the frontrunners in Europe for implementing this legislation, which puts patients’ safety at the heart of the process” (see press release).
The Virgin Health Bank, which - unlike most commercial cord blood storage facilities - requires donors to make a portion of each blood sample publicly available (see previous news). has objected to the move, saying: “We already know that there is a critical shortage of cord blood units and there is little incentive for NHS Maternity units to apply for these licenses which may result in further constraint on the availability of cord bloods for lifesaving transplants” (see press release). Notably, procurement centres that do not already hold a suitable HTA licence will probably be charged a licence fee: 2007/8 HTA fees are £7600 for new applications, and £1000 for additional licences for the same centre (see HTA licence fees).
11 May 2008Researchers from St George's Hospital, London, have announced that they have identified seven different subtypes of chronic fatigue syndrome (CFS), also known as Myalgic Encephalopathy (ME) and post-viral fatigue syndrome.
It has been estimated that some 250,000 people in the UK are affected by this illness (for more information, see the ME Association) but it is very difficult to diagnose, due to the wide spectrum of clinical symptoms and severity experienced by different patients in addition to extreme, chronic fatigue that is not alleviated by rest. Despite the availability of diagnostic criteria, definitive diagnosis of CFS/ME remains elusive, and is essentially reached by the exclusion of other potential underlying conditions. There is a lingering belief among some clinicians that the disease is a purely psychological phenomenon, but evidence of a biological basis is mounting steadily.
The new study was based on genetic analysis of 55 patients and 75 healthy blood donors; researchers reported to a conference in Cambridge last week that they have identified seven distinct subtypes of CFS/ME typified by specific genetic patterns, linked to specific symptoms. For example, the most common forms were linked to moderate levels of body pain and sleep problems (type four), and fatigue (type six), whilst other forms showed different symptoms such as stomach problems and muscular weakness (type five), and anxiety, depression and pain (type one).
Comment: Although the results from such a small study will require confirmation in a much larger cohort of subjects, researchers hope that the work may lead to a diagnostic test for the condition. Neil Abbot, of ME Research UK commented: "It's a hard illness to get a handle on, so a clinical test would be the single best way forward for everyone" (see BBC news). Previous research has shown that genetic analysis can identify specific sub-types of cancer, potentially allowing much more precise diagnosis, prognosis and clinical management; now it seems possible that genomic information could aid diagnosis in other complex conditions that involve significant genetic contributions to pathology.
9 May 2008The US Genetic Information Nondiscrimination Act (GINA) has finally obtained congressional approval after several previous attempts failed on their way through the Senate and House of Representatives (see previous news). The United States Congress is the bicameral legislature of the federal government of the US, consisting of two houses, the Senate and the House of Representatives, to whom senators and representatives are directly elected. The legislation was unanimously (95 votes to 0) approved by the Senate on 24 April 2008 and passed in the House of Representatives on 1 May 2008, by a vote of 414 to 1 (sole dissenter being Congressman Ron Paul). It is anticipated that President Bush, who has expressed public support for the legislation, will sign the bill soon.
The long-awaited legislation, which has been debated in Congress for 13 years, requires equity in the provision of mental health and substance-related disorder benefits under group health plan and prohibits discrimination on the basis of genetic information with respect to health insurance and employment. It prevents insurers from refusing to provide health insurance to healthy people on the sole basis of genetic predisposition to a disease; it also prohibits them from requesting or using information from genetic tests in the pricing of long-term care insurance. Employers are also denied the right to request or use genetic test information in the process of employment of individuals or in the promotion or dismissal of staff.
Substantive and procedural objections were raised to the previous version of the approved legislation, bill H.R. 493, proposed in conjunction with the Paul Wellstone Mental Health and Addiction Equity Act of 2007 and passed the House on 25 April 2007 by a vote of 420-3. It was noted that there was no clear “firewall” between the provisions on genetic discrimination in health benefits provided by health insurers and plans, and those that addressed genetic discrimination in employment; further definition was sought in the relationship of the bill to other provisions of law, including various types of remedies; and it was felt that the bill might unintentionally permit “forum shopping.” There was also a concern that in the absence of clarification, the bill might be construed to prohibit health plans and issuers from using information about the manifested disease of a dependent covered by an individual plan for appropriate and routine insurance purposes. Nevertheless, the need for nondiscrimination legislation was affirmed as critical to the realization of the full potential of genomic medicine.
The US predicts that the new law will enable people to take full advantage of the promise of personalised medicine without fear of discrimination based on their genetic information, and could also improve the climate for medical research. The UK observes the US legislative process with interest, as a similar debate about the appropriateness of genetic nondiscrimination legislation becomes increasingly apparent in this jurisdiction (see previous news).
7 May 2008A working group of the European Society of Human Genetics (ESHG) has brought out new recommendations on the patenting and licensing of genetic tests [Aymé et al. (2008) Eur. J. Hum. Genet. 16: S3-S9]. The recommendations are accompanied by a background paper covering the associated ethical, legal and social issues [Soini et al. (2008) Eur. J. Hum. Genet. 16: S10-S50].
Whilst it is generally recognised that patents can be beneficial for society, if they drive innovation and progress, they can also be problematic particularly in the field of genetics and genetic testing. Part of the problem is that identification of a gene or mutation associated with a particular trait is not an invention but a discovery, which is not patentable according to the European Patent Convention (EPC). Nonetheless, despite strong public and scientific opinion against the principle of patenting life, estimates suggest that patent applications have been filed for nearly 20% of human genes (see previous news story).
Genetic testing is an increasingly important part of medicine, and the proper use of patents for genetic tests should promote innovation and better healthcare services through a fair reward for the inventors. Indeed, the prospect of IP protection is one of the factors that drive translational research in the field of medical genetics. For example, patenting of novel technologies for genetic testing, such as PCR and microarrays, promotes investment whilst still allowing innovation around the technology. However, once a gene-disease association has been proven, the relative ease with which a novel test can be developed using a current technology platform make the patentability of the genetic test itself significantly more complicated.
The ESHG have reconciled these viewpoints with respect to genetic testing by recommending that:
(1) the breadth of the claims in genetic patents should be limited; for example, by limiting the patent on use of a test to a specific disease, as occurred in the case of the Myriad BRCA1 patent for breast cancer (see previous news story)
(2) the number of patents should be reduced by limiting the patentable subject matter; for example, by prohibiting patenting of specific gene variants
(3) a professional or scientific body should issue an annual statement on the obviousness/ non-obviousness to increase the quality of granted patents
(4) the concept of utility in patent law be redefined to take account of downstream clinical experience (i.e. clinical validity and utility associated with testing).
Regarding licensing, the ESHG concluded that licenses should be non-exclusive and easily obtainable, as is currently outlined in the Economic Organisation for Cooperation and Development (OECD) guidelines. The ESHG also recommended that the European Patent Office (EPO) consider having an ethics committee to deliberate issues of major interest, such as patents applied to genes.
7 May 2008An EU funded project to design a tool for diagnosis and monitoring of coeliac disease is underway (see news source). The collaborative project named CD-MEDICS ('Coeliac disease management monitoring diagnosis using biosensors and integrated chip systems') will be an interdisciplinary venture aimed at developing a lab-on-chip device which can be used at the point-of-care to screen blood samples for genes which make people more susceptible to developing coeliac disease as well as auto-antibodies which can indicate disease status.
Coeliac disease is an autoimmune disease, also known as gluten intolerance, for which the treatment is strict adherence to a gluten free diet. Although it is estimated to affect around 1% of the population, it is thought to be significantly under diagnosed as the disease may present at anytime in a person’s life and can be difficult to diagnose due to a wide range of associated symptoms and their similarity to symptoms of other diseases. It is a polyfactorial disease, although there is a heritable component and genetic factors have been identified which contribute to increased risk of disease. However, it is not always the case that people possessing susceptibility genes will develop the disease. Absolute diagnosis requires antibody screening and a small bowel biopsy.
This device will form an efficient way to identify at risk individuals and monitor them, as early detection and treatment can help reduce the adverse effects of the disease. It may also negate the need for invasive diagnosis and will allow monitoring of patients who already have the disease in order to ensure that they are complying with a gluten free diet.
Whilst point-of-care tests for coeliac disease are already available, they usually only measure the antibodies associated with the disease. It is hoped that the addition of a genetic test to this panel will help to identify pre-symptomatic high risk individuals, although the clinical utility of this approach is currently unclear.
The programme involving various institutions in 10 countries will be sponsored for four years under the seventh framework programme (FP7). It is hoped that the technologies developed under this programme could be applied to other health conditions such as diabetes and rheumatoid arthritis.
14 May 2008An international collaborative genome wide association study looking at insulin resistance and related phenotypes has identified a gene sequence linked to an expanding waist line (central adiposity), weight gain and insulin resistance, which can lead to type 2 diabetes (see BBC news). The results of the study published in Nature Genetics identified four single nucleotide polymorphisms (SNPs) associated with waist circumference; of these the rc12970134 sequence was found to have a strongest association with waist circumference [Chambers et al. (2008) Nat. Genet. doi: 10.1038/ng.156]. The sequence was also shown to be associated with insulin resistance, in a manner that is partially independent of adiposity.
Individuals who are homozygous for the risk allele rc12970134 had a ~2cm greater waist circumference and ~10% higher homeostasis model assessment of insulin resistance (HOMA-IR) results. The study also shows that there is a higher frequency of this risk allele in individuals of Indian Asian ancestry in comparison with those of European ancestry. This finding suggests a genetic mechanism contributing to the higher incidence of obesity and insulin resistance among Indian Asians.
All four SNPs identified in the study were found to be located near the MC4R gene, which is thought to be involved in regulating energy levels in the body. Mutations in this gene leading to a loss of function are associated with severe childhood obesity and hyperinsulinaema. Another study published in the same journal has identified other common variants near the MC4R gene that appear to influence fat mass, weight and obesity risk [Loos et al. (2008) Nat. Genet. doi: 10.1038/ng.140]; these variants have an additive effect to those of the FTO gene (see previous news). How these common variants influence the MCR4 gene is not known and a greater understanding of these factors may give an insight into the pathogenesis of both rare monogenic subgroups and the common multi-factorial forms of obesity.
Comment: The pathophysiology of obesity and related conditions that may contribute to metabolic syndrome, such as hypertension (high blood pressure), insulin resistance, central adiposity, raised levels of triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol in the blood, is known to be highly complex, and to involve multiple genetic and environmental factors. However these conditions, which are increasingly prevalent in countries such as the UK and US, significantly increase the risk of cardiovascular disease and type II diabetes, and represent a major public health problem. These recent papers represent another piece in the jigsaw puzzle in trying to understand the genetic and molecular basis of the disease, with a view to providing new ways in which to combat it. Many major reserach programs are also focused in this area. For example, pharmaceutical company Pfizer recently formed a consortium with four US universities and another company to use a systems biology approach to improve understanding of diabetes and obesity. The three-year Insulin Resistance Pathway (IRP) Project will look at insulin signalling in fat cells (see press release).
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