In the news

The government, after discussions with members of the scientific and medical research communities, has tabled a series of amendments to the Human Tissue Bill (see newsletter article December 2003). The amendments have elicited positive comments from stakeholders who have had concerns that the Bill, as originally drafted, would have seriously impeded medical research. The Bill was created to prevent another organ retention scandal like that at Alder Hey Children’s Hospital. However, critics felt the Bill went too far. For example, they saw the Bill as attempting to outlaw the use of any human tissue without the explicit consent of the patient. Such a requirement could cause serious obstacles for researchers studying disease, such as limiting the amount of tissue available. However, some key parties see the changes tabled by the government as answering this and other concerns. Dr Mark Walport, Director of the Wellcome Trust told the BBC, “We now have a proper and sensible balance between protecting the rights and confidentiality of patients and their families, and the need to safeguard research that will provide benefits for health in the future.” However, the final wording of the Bill is still yet to be decided; the Bill will have its third reading in Parliament on Monday, 28 June.

An Italian businessman has advertised paternity test kits offering ‘peace of mind’ for men who wish to determine whether they are the biological father of a child. For around £470 ( 700) a kit is provided for taking swab samples from the child and putative father; these are sent to a laboratory for testing and results sent out by post or email. Such kits are already available in the US and some European countries including the UK, but they are banned in France and in Belgium strict regulations exist to ensure that consent from both parents is obtained. The Italian Society of Human Genetics has posted a response to the advertisements condemning the use of such tests, citing the necessity for informed consent of all parties and, in the case of children, the consent of both legal parents. Consent of both parents for paternity testing of children is not legally required in the UK. The Human Genetics Commission (HGC) is currently collating information on paternity testing services in the UK and how far they comply with the Department of Health’s Code of Practice and Guidance on Genetic Paternity Testing Services.

It was announced today that the MRC will provide £1.5 million in funding to establish the MRC Cambridge Centre for Stem Cell Biology and Medicine as the core of the Cambridge Stem Cell Institute (see MRC press release). The University of Cambridge has already contributed £10 million for the new interdisciplinary centre to be established as a centre of excellence in stem cell genetics, biology and medicine, with the aim of harnessing knowledge to develop stem-cell based treatments for human diseases such as diabetes, multiple sclerosis, Parkinson’s and Alzheimer’s diseases.

The new MRC Centre, which is co-funded by Juvenile Diabetes Research Foundation (JDRF) and will be directed by Professor Roger Pedersen, is intended to facilitate the movement from basic stem cell research to clinical applications. Other key researchers at the centre will include Professors Azim Surani, Anne Cooke, Charles ffrench-Constant, Tony Green and Dr Sarah Bray. Research at the Centre will focus on understanding the genetic and cellular mechanisms involved in the ability stem cells have for self-renewal and growth into any kind of body tissue, and on developing stem-cell based therapeutic measures to replace cells that have been lost due to disease.ss

Welcoming the MRC funding, Professor Pedersen said: "Stem cell research has a profound potential for treating currently debilitating diseases…and thus has the capacity to markedly improve the quality of life", whilst Professor Alison Richard, Vice-Chancellor of the University of Cambridge, commentsed: "The research of these scientists is of immense medical significance, and I am confident that it will bring breakthroughs of huge benefit for human health and well being" (see University of Cambridge press release). The MRC Cambridge Centre for Stem Cell Biology and Medicine will form part of co-ordinated research programmes in stem-cell research the UK.

A team of scientists from Monash University in Melbourne, Australia, have developed a new technique for genetic testing of embryos, based on microarray technology. Microarrays, also known as gene chips, are systems that enable the rapid and simultaneous analysis of thousands of DNA sequences. The researchers have found that they can be used for pre-implantation genetic diagnosis (PGD) of cystic fibrosis. Cystic fibrosis (CF), an inherited disease that affects the lungs and digestive system, is the most common life-shortening genetic disorder in the UK, with an overall birth prevalence of about 1 in 2500. Around 1 in 25 people carry a gene with a cystic fibrosis mutation; if a baby inherits one such gene from each parent then it will have the disease. The identification of embryos affected by and free from cystic fibrosis is one of the current uses of PGD.

The advantage of using microarrays is that multiple different mutations can be screened for at once. Although there is a single very common mutation associated with Cystic Fibrosis (the Delta F508 or ÄF508 mutation), there are many other less common mutations that can cause the disease, some very rare. Presently, parents may have to wait several weeks for embryos to be screened for a selection of the most common mutations. Ms Chelsea Salvado, a member of the Monash research team, is reported as having said: "Microarray technology will lead to semi-automated genetic testing for both PGD and prenatal diagnosis, providing a rapid diagnosis, thus reducing the stress of couples waiting for a result…The introduction of microarray technology could lead to PGD being offered for all genetic diseases in the future” (see BBC news report). Microarrays could also be used in prenatal testing for cystic fibrosis and other genetic disorders.

The technique, presented by the Australian researchers at the Annual Meeting of the European Society of Human Reproduction and Embryology in Berlin this week, requires the use of ten cells removed from embryos of between five and six days old, when the embryos have around 100 cells. At present most PGD tests are performed using single cells taken from three-day old embryos, which have eight cells in all, but the method of DNA amplification was not reliable for a single cell from these younger embryos.

Health Minister Lord Warner announced today that £4 million of funding will be devoted to pharmacogenetic research. The awards are part of the funding strategy announced in the Genetics White Paper last year (see newsletter article June 2003). The winning bids come from six institutions, primarily in the north of England. Their research projects all examine patients’ genetic susceptibility to specific drugs, the aim of pharmacogenetic studies.

In the future it is hoped that, based on a person’s genetic makeup, doctors will be able to determine how that individual will react to a certain drug or drug dosage. With this knowledge, patients can be prescribed a specific drug or treatment that will be effective for them that will avoid adverse reactions, so-called personalised medicine. While the research that will produce such individualised treatment is still in its infancy, with some critics believing it will never become reality, the government is committed to translating genetic advances into patient care. As Lord Warner stated, "This is part of the government’s commitment to make sure that NHS patients get the full benefit of the latest developments in genetic knowledge.”

The funded projects will focus on different drugs and their reactions in patients. In Salford, researchers will examine whether genetic factors have a role in creating the adverse reactions some patients experience when taking the drug Azathioprine, used to treat inflammatory diseases. In Liverpool, researchers will study whether genetics and environmental factors play a part in the bleeding suffered by some patients taking the drug Warfarin. It is hoped that millions of patients in the future will benefit from these and the other funded studies. A full list of the research projects is available as part of Lord Warner’s press announcement.

The Human Fertilisation and Embryology Authority (HFEA) has announced new guidelines aimed at providing better protection for frozen sperm, eggs and embryos stored at fertility clinics. The guidelines are designed to help prevent incidents of samples being lost due to incorrect storage procedures. If samples are held at too low a temperature they can be rendered unusable. In June 2003, a freezer fault at Southmead Hospital in Bristol caused the loss of sperm samples from 28 men who had stored their sperm prior to cancer treatment. The men, if rendered sterile by their cancer treatment, may now not have another opportunity to have children of their own.

The guidelines require all clinics storing frozen sperm, eggs and embryos to have in place by June 2005 new warning procedures in case of a storage emergency. Alarms and monitoring systems must be fitted to storage vessels. An out-of-hours alarm system to alert staff must be in place, with staff on call to deal with the emergency. The guidelines also state that patient samples should be spread between storage vessels, to ensure that some of the person’s material is protected if one vessel breaks down. While welcomed, there is a question of whether the new storage guidelines will be helpful. Dr Peter Bromwich, a consultant gynaecologist at the London Fertility Centre, noted to the BBC that, “when systems fail, they very rarely fail gradually, but usually catastrophically, and even if you were in the room at the time you might not be able to do very much about it.”

The guidelines are one of a series of HFEA initiatives to improve patient and sample safety. The HFEA has recently formalised an incident alert system that involves the sharing of anonymous adverse reaction data so that clinics can learn from one another and help prevent the reoccurrence of mistakes.

The Human Fertilisation and Embryology Authority (HFEA) will consider today the first application to license work to clone human embryos to treat disease. Researchers from Newcastle have applied to use the technology that created Dolly the sheep, cell nuclear replacement (CNR), to clone the embryos. In CNR, the nucleus is removed from an unfertilised egg and replaced with DNA from the donor. The egg is then stimulated as if it were being fertilised; the resulting embryo is cultured to the stage where it starts producing stem cells. The stem cells will be genetically identical to the donor and can then be implanted without fear of rejection. In the Newcastle study, if successful, the stem cells will be used to explore future treatments for diabetes. Future applications may include treating those with other conditions such as spinal cord damage.

In order to create stem cells that are genetically identical to the donor, embryos must be cloned rather than using existing embryos. Cloning human embryos for therapeutic purposes is legal, however, the procedure is similar to that of reproductive human cloning (cloning to make another human being), which is illegal in the UK. This has caused opponents to send letters to the HFEA asking that they reject the license application. They fear that the information gained from the research will not produce effective therapies but will provide information to those who wish to clone human beings. As Dr David King, from the pressure group Human Genetics Alert, told the BBC, “This research is a waste of public money, and crosses important ethical lines for the first time.” Others disagree. Alistair Kent, Director of the Genetics Interest Group, believes the research is necessary. "If we don't do the research, and it does have the potential, then we are not only ignoring the needs of those who are alive now, but also all future generations as well." The HFEA is expected to announce its decision next week.

A judge in Italy ordered that a couple undergoing IVF treatment had to implant all the embryos created, regardless of any genetic condition the embryos might carry. Under Italian law made earlier this year (see newsletter article February 2004), reproductive techniques are restricted. The law bans freezing and destroying embryos and all embryos created by IVF, limited to three oocytes, must be implanted into the woman. The couple in this case both carry the recessive gene for ß thalassaemia and had wanted to have pre-implantation genetic diagnosis to determine which embryos were healthy, as they did not want to have to abort the pregnancy, and decided to challenge the law on this point. They lost their case and were required to implant the embryos. The British Medical Journal reported that the judge stated that, “…according to the new law, the woman did not have the right to choose to have a healthy baby” (BMJ 2004 328, 1334). Shortly after the transfer, the woman suffered a haemorrhage and lost the embryo, which was later shown to be healthy. The woman claims that the haemorrhage was likely brought on by stress.

The strict fertility law is also being blamed for driving non-sterile couples out of Italy to other countries for treatment, as the law limits any fertility treatment to couples proven sterile. The BMJ notes that specialists and researchers in the field are also leaving. In addition, centres are reporting that success rates in women over 35 are dropping and multiple pregnancies in women younger than 35, who are often implanted with three embryos, are increasing.

The National Institute of Clinical Excellence (NICE) and the National Collaborating Centre for Primary Care (NCCPC) have today released a set of guidelines relating to the classification and care of women at risk of familial breast cancer. The guidance states that women calculated to have a low risk of developing breast cancer (lifetime risk of less than 17%) should normally be cared for in primary care; those found to have a moderate level of risk (lifetime risk of 17-30%) should generally be cared for in secondary care, and those at high risk should receive tertiary level care. High risk is defined as a calculated lifetime risk of 30% or greater, or a 20% or greater chance of a faulty BRCA1, BRCA2 or TP53 gene in the family. Protocols for the management of women at each level of care are set out in the guidelines.

It is proposed that women’s family histories should be taken and risk assessments made in primary care, with appropriate systems in place for the referral of women with moderate-high risk. Key messages that healthcare practitioners should get across to women who are concerned by a family history of breast cancer are highlighted, including that the great majority of women with a family history of breast cancer do not fall into a high-risk category and do not develop breast cancer, and that the great majority of women with a relative with breast cancer are not at substantially increased risk of breast cancer themselves.

The importance of providing patients with both standard written and individually tailored information (including access to psychological support and assessment where appropriate) to allow them to make informed choices and participate in decision-making is underlined. Another key recommendation in the guidelines is that women should be made aware that genetic testing is appropriate only for a small proportion of women who are from high-risk families.Genetic testing should be offered in the context of tertiary care to women who have a 20% or greater chance of a BRCA1, BRCA2 or TP53 mutation in the family and an affected relative available, after two sessions of pre-test genetic counselling. A costings report accompanying the guidelines notes that the main issues with respect to genetic testing in tertiary care are the current backlog of tests, insufficient capacity and a lack of information about specific levels of funding for BRCA1 and BRCA2 testing. Funding made available centrally under the Genetics White Paper to expand and modernise genetic laboratory capacity is anticipated to be sufficient to permit implementation of the guidelines. It is estimated that a one-off cost of £2.2 million would be required to clear the backlog, and a one-off cost of £1.55 million would result from the anticipated increase in women requiring genetic testing. The ongoing annual cost of providing genetic tests to women at high risk is estimated to be £825,000 with a further £440,000 required for the provision of psychological support.

The Department of Health has recently revealed plans to involve pharmacists in the Government’s public health strategy. Contracts have been awarded to four organisations (Pharmacy HealthLink, The Royal Pharmaceutical Society of Great Britain, the Faculty of Public Health and the UK Public Health Association) to form a consortium to work with pharmacists in exploring how they can make greater contributions to public health (see press release).

Announcing the award of these contracts, Minister of State for Health Rosie Winterton said, “The track record of community pharmacists… is evidence of how integral they are to tackling public health issues. But we would like pharmacists do even more and get involved in aspects of care such as checking people's blood pressure and even measuring blood glucose levels. This consortium will help to maximise the contribution of pharmacists, their staff and the premises in which they work, playing a part in helping people enjoy healthier lives by giving them access to more information about their health care”.

It is likely that pharmacists will play a major role in the eventual implementation of pharmacogenetics in the NHS; pharmacogenetics refers to the relationship between genetic variation between individuals and the safety and efficacy of drugs. In the future, it is hoped that pharmacogenetic profiling will allow the selection of the optimal drug and dose to benefit each patient, and prevent many adverse drug reactions. A White Paper on Public Health is to be published later this year, and will include the emerging public health role of pharmacists.

An expert group has been formed to review NHS genetic services and the application of new genetic knowledge in Scotland, to make sure that the NHS in Scotland continues to keep pace with advances in genetics and their healthcare applications. Scottish Health Minister Malcolm Chisholm commented: "The findings and recommendations of the Group will provide a framework within which we can plan and develop our genetic services and maximise opportunities for advances in genetic knowledge to be used to enhance other services currently being offered by the NHS" (see press release).

The group, which will meet for the first time at the end of June, is to be chaired by the former Chief Medical Officer of Scotland, Professor Sir Kenneth Calman. Their intention is to review current genetics services in the light of the Genetics White Paper of June 2003 (‘Our Inheritance, our future – realising the potential of genetics in the NHS'), to consider how current standards can be maintained for existing genetics services and to assess the potential impact of developments in genetics harnessed for the benefit of academia, the biotechnology industry and the NHS in Scotland.

Sperm donors in the Netherlands are no longer allowed to remain anonymous, due to new legislation, and as a result, donations have dropped. The new law gives children born using donated sperm the right to obtain information about their biological father at age 16. In response, the number of donors has decreased and women are now facing a wait of up to two years at one Dutch sperm bank. Anecdotal evidence shows that women are crossing the border to Belgium for treatment, getting sperm from a friend, or using the internet to find treatment on the black market.

Belgium officials have considered adopting the same stance of ending anonymity but no changes are currently planned. The UK Department of Health announced in January that, after April 2005, the UK will end anonymous donations with donor information being available to children when they reach 18 years of age (see newsletter article January 2004). The Human Fertilisation and Embryology Authority (HFEA) has endorsed the plan. They note that when donor anonymity was removed in Sweden, the number of donors dropped at the beginning but then returned to a normal level. The HFEA expects this to be the case in the UK. Whether the number of Dutch donors will rebound remains to be seen.

Scientists at a private US fertility clinic have created embryonic stem cell lines from embryos with genetic defects. Researchers from the Reproductive Genetics Institute in Chicago presented their work at the second annual meeting of the International Society for Stem Cell Research in Boston last week. The embryos were reportedly donated by couples undergoing pre-implantation genetic diagnosis (PGD) at the clinic to avoid the birth of a child with a genetic disorder; embryos affected by these conditions would normally be discarded. Twelve embryonic stem (ES) cell lines have been established with a total of seven different genetic defects: myotonic dystrophy, Duchenne muscular dystrophy, neurofibromatosis type 1, Fragile X and Marfan syndromes, beta-thalassaemia and Fanconi anaemia. These are the first ES cell lines to be derived from embryos with specific genetic diseases; it is hoped that they may be useful for studying the diseases in question and developing new treatments.

Yury Verlinsky, president of the Reproductive Genetics clinic, has said that these and other new stem cell lines will be made available to other scientists engaged in privately funded research. Current restrictions in the US prevents federally funded researchers from using new stem cell lines, limiting them to cell lines in existence in August 2001 when the restrictions came into force. Reproductive Genetics scientists plan to create more cell lines from embryos affected by different genetic diseases.

Support for stem cell research has been boosted in the US as a result of the death of former US President Ronald Reagan. Reagan, aged 93, died on 5 June from Alzheimer’s, after a ten-year battle with the disease. As a result, patient groups and US senators are announcing their support for loosening the restrictions on stem cell research put in place by President Bush. A majority of senators, 58, sent a letter asking for a change in policy to the White House soon after President Reagan’s death. Nancy Reagan had made her support for the research clear in comments made publicly last month. There have been no moves by the White House to respond to the increased pressure; officials continue to state that the policy is fair and that research that falls outside of federal policy can continue in the private sector.

While the increased support for stem cell research is welcomed, some experts warn that a treatment for Alzheimer’s may be slow in coming, while treatments for Parkinson’s and diabetes may be realised more quickly. Alzheimer’s is a very complex disease, involving billions of nerve cells, and the process of cellular replacement of the damaged cells will be difficult. As Lawrence S.B. Goldstein, an expert from the University of California at San Diego, stated in the Washington Post, “We don’t even know what are the best cells to replace initially.” The Alzheimer’s Society acknowledges that Alzheimer’s patients may not be the first to benefit from new treatments discovered by this science. Their web site notes, “In the short to medium term, the benefits of further stem cell research may be to strengthen our understanding of Alzheimer’s disease and use this information to develop further treatments for Alzheimer’s.”

UK Biobank has published a consultation paper detailing its proposals for how samples collected as part of the project will be managed. The consultation is open for comments until 6 August. The report is the work of the UK Biobank Sample Handling and Storage Scientific Committee Sub-group on Sample Storage. The group first met in December 2003 and has been looking at the science and processes involved in the banking of DNA samples. Their report, listing recommendations on the management of samples within the Biobank project, is seen as one of the most comprehensive on the subject that has yet been produced.

The aim of the UK Biobank project is to better understand how genetic and environmental factors impact our health. Volunteers aged 45-69 will donate blood and urine samples, complete a questionnaire on their lifestyle and have measurements taken. The participants will then be followed over the years, with additional information about their health and lifestyle collected. The data compiled will enable researchers to study factors that cause disease in later life.

In their report, the Scientific Committee Sub-group details specific procedures they recommend for the appropriate handling and storage of participants’ samples. For instance, they recommend the use of high-throughput industrial scale operations and robotics to manage the samples. Each participant’s sample should undergo a series of biochemical tests that will aid the study of diabetes, heart and liver disease and blood and metabolic disorders. Other studies may be added to this list and the scientific group welcomes suggestions from those responding to the consultation. The samples should be stored in such a way as to maintain their long-term integrity and all samples will be transported to the central processing facility in Manchester.

This report is only one of the several expected from UK Biobank Scientific Committee sub-groups. The other sub-groups are considering recruitment procedures, the questions to be asked of patients as well as the measurements to be taken, and data management issues. Once the consultation period on this particular report is completed, a revised report will be published. UK Biobank officials expect the first pilot studies to test the procedures in the report to begin in late summer 2004, providing ethical approval is obtained.

Research Councils UK has announced that it has awarded grants totalling £16.5 million to universities in the UK for a variety of stem cell research projects. There have been 57 grants funded to eighteen different universities. Five of the UK’s research councils have provided the funds: the Medical Research Council (MRC), the Biotechnology and Biological Sciences Research Council (BBSRC), the Economic and Social Research Council (ESRC), the Engineering and Physical Sciences Research Council (EPSRC) and the Council for the Central Laboratory of the Research Council’s (CCLRC).

The investment aims “…to speed the development of new treatments and cures from the laboratory to the clinic” and the projects cover many aspects of stem cell research. Some projects will focus on developing new treatments for major diseases and disabilities, such as spinal injuries, diabetes, heart disease, Alzheimer’s and Parkinson’s disease. For example, Dr Geoffrey Raisman, of the National Institute of Medical Research in London, will take stem cells taken from the lining of the nose and use them to attempt to repair spinal cord damage in humans. Trials in rats have already shown promise. Other projects aim to learn more about how stem cells function, such as how they differentiate to become different tissues. Money granted to the University of Sheffield will go to establishing a Human Embryonic Stem Cell Resource Centre, led by Prof Peter Andrews. The centre will provide access to expertise, resources, facilities and training in the field. Improvements in research skills and standards will lead, it is hoped, to a reduction in tissue use.

These grants are yet another signal of the lead the UK is taking in the area of stem cell research, after the opening of the UK Stem Cell Bank earlier in May (see newsletter article May 2004). As stated by Research Councils UK, these “…strategic grants will ensure that the UK is at the forefront of the international research community working on stem cells, and is in a position to lead on the considerable health and economic implications the field promises in the future.” Their announcement also notes that the Economic and Social Research Council will be funding additional grants covering “…the governance, innovation and social transformation issues related to stem cell technologies.” In addition, they will be outlining their future plans for looking more closely at the social science issues underlying stem cell research.

More information about the grants that have been funded and contact information for the research councils involved can be found in the Research Councils UK press announcement.

The Wales Cancer Bank (WCB) was publicly launched in Cardiff today. The WCB is an all Wales initiative to create a tissue bank of samples from patients in Wales with possible or confirmed cancer. Eventually, it is hoped that all patients in Wales who are undergoing an operation to remove tissue where cancer is a possible diagnosis will be participants in the bank. Those involved believe the WCB will be unique as it will be the first such centre to collect samples on a national scale.

The All Wales Research Ethics Committee has approved the creation of the WCB. All patients will be asked for their consent to participate. Normal and cancerous tissue will be collected and correlated with clinical outcome information for the patient. The information can then be used in large-scale studies where hundreds of samples are needed to find meaningful results. As Health Minister Jane Hutt explained, “The aim is to achieve a greater understanding of cancer and to be able to provide better treatments for patients with cancer. This initiative clearly demonstrates our commitment to developing a scientific evidence base to form the basis of our fight against cancer.” The WCB also sees the bank encouraging biotechnological development in Wales.

Four NHS Trusts in Cardiff, Swansea, Haverfordwest and Bangor will pilot the project. The WCB will also work in conjunction with other similar projects in Europe. It has received endorsement from patient support groups and celebrities such as Huw Edwards and Ioan Gruffudd.

Alzheimer's disease (AD) is a progressive neurological disease in which there is gradual loss of the nerve cells in the cerebral cortex of the brain causing serious mental deterioration. It is the most common form of dementia, with an average lifetime risk of about 10-12%. The genetic basis of Alzheimer’s has been extensively investigated, based on rare familial forms of the disease, although the vast majority of AD cases are sporadic and not inherited. Mutations in three genes have been found associated with the familial forms of early onset AD: the amyloid precursor protein (APP), pre-senilin 1 (PSEN1) and pre-senilin 2 (PSEN2) genes; the common polymorphic APOE4 allele has also been associated with a modestly increased risk of Alzheimer’s. However, no genes have been associated with sporadic cases of early onset (or the more common late-onset) forms of AD. A paper in this month’s edition of Human Molecular Genetics reports on a case of somatic and germline mosaicism in a patient with sporadic early-onset AD [Beck JA et al. (2004) Hum Mol Genet. 2004 13, 1219-1224]. Mosaicism refers to a phenomenon whereby an individual has two or more different cell lines within their body with different genetic content. It has previously been suggested that mosaicism for trisomy of chromosome 21 might cause AD, because of the known association between Trisomy 21 (Down’s Syndrome) and early onset AD. Patches of cells in the brain with additional copies of chromosome 21 might cause these changes in individuals who do not have Down’s.

The paper reports a woman who presented with a neurodegenerative disorder, confirmed as early onset AD by autopsy after her death age 58. The woman’s daughter then presented at age 27 with very different neurodegenerative symptoms. Analysis of DNA from the daughter’s blood identified a P436Q mutation in the PSEN1 gene, but the mutation was not present in DNA from the mother’s blood. However, when DNA from the mother’s cerebral tissue was sequenced, the P436Q mutation was identified. A subsequent, more sensitive analysis of blood cell DNA found low levels of the mutation were present after all. Further investigations revealed the existence of three different alleles in the original patient, two wild-type and one mutant, indicating the existence of somatic (non-reproductive cell) mosaicism. Haplotype analysis of three of her children showed that the two unaffected children had inherited wild-type alleles whereas the affected daughter had inherited the mutant allele, meaning that the original patient showed mosaicism in both somatic and germ cells.

The authors claim this to be an important finding on the basis that patients with sporadic AD may have somatic cell mutations that are expressed in their neural tissue, causing the disease, that are undetectable by normal analysis of DNA from the blood. The frequency of cases of sporadic AD that may be caused by somatic mosaicism affecting brain cells is not known; to estimate this it would be necessary to detect mutations in post-mortem cerebral tissue. In the original patient, the degree of mosaicism for the mutant allele was calculated to be 14% in the cerebral cortex. It is presumed by the authors that this relatively low degree of expression of the mutant allele accounts for the later onset and different symptoms of disease compared with those of the affected daughter, who died at age 39. They suggest that even very low levels of mosaicism could cause clinical disease within the expected lifetime of a patient, and hence account for a proportion of not only early-onset sporadic AD cases, but also of the much more common late-onset AD, and possibly other late-onset neurodegenerative disorders too.

Comment: This paper raises the possibility of a new genetic factor involved in the pathology of a common disease that represents a significant public health burden in developed countries such as the UK. Further research into the incidence of somatic cell mosaicism in post-mortem cerebral tissue from patients with AD and similar diseases is strongly indicated, to determine the extent of this phenomenon. If it is found to account for a significant proportion of cases, this may influence research into potential new therapies for these diseases.

For more information on the genetics of Alzheimer's Disease, see the disease profile from our information resource pages.

Prostate cancer represents the most common cancer among British males, with around 27,000 new diagnoses and 10,000 deaths every year. The diagnostic test for prostate cancer, which measures levels of the prostate specific antigen, cannot determine the severity of the tumor. Recently, an article published in the journal Oncogene has suggested an association between levels of the transcription factor E2F3 and both the development and prognosis of prostate cancer. E2F3 plays a role in regulating the expression of the Enhancer of Zeste Homolog gene 2 (EZH2). This current work builds on a previous observation that increased levels of EZH2 were associated with a poorer prognosis in prostate cancer patients. In addition, EZH2 has been suggested to be associated with several other malignancies, including breast and colon cancer. The findings of this most recent study have been widely reported online by both The Times and Independent newspapers, and by the BBC and Reuters news agencies.

Researchers at the Institute of Cancer Research and the University of Liverpool investigated whether the expression of E2F3 was associated with prostate cancer, and disease progression, in tissue samples from patients and disease-free controls. Over-expression of E2F3 has previously been shown to be associated with both tumour grade and stage in bladder cancer. High levels of E2F3 were found in two-thirds of prostate cancers compared to just 2% (a single sample) among controls. In addition, the authors present evidence for E2F3 expression being a prognostic factor in predicting individual risk of death from prostate cancer with increased expression of E2F3 being associated with decreases in survival among patients.

Comment: The development of a reliable prognostic test for prostate cancer would prove an invaluable tool in managing the treatment of individual patients. The authors of this recent study suggest a potential prognostic role for E2F3 in prostate cancer, showing an association between levels of E2F3 expression and mortality among prostate cancer patients. The authors draw firm conclusions from their data, however, the relatively small number of prostate cancer cases (n=147) and controls (n=43) would suggest a more cautious interpretation of these findings until replicated in a larger study.