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An increasing number of studies are taking place with the aim of identifying the genetic basis of common conditions that have a have a major public health impact such as cardiovascular disease, various cancers and obesity. Such studies are expected to increase understanding of disease processes and lead to more effective treatment options, but it is likely that it will take time before such clinical benefits are achieved.

 

Another area of medicine that is likely to benefit from genomic and biomolecular advances is the development of more accurate ways to diagnose and screen for various conditions, based on genetic and biomarker profiles. It is hoped that this latter approach will provide less invasive, more convenient routes to diagnosis and treatment. It is also much closer to clinical application and, in some cases, is actually in clinical trials, as demonstrated in three studies reported earlier this week.

 

One study combines analysis of gene expression patterns in biopsy samples from a fatal brain tumour called glioblastoma multiforme (GMB) with detailed imaging of patients’ brains using magnetic resonance imaging (MRI) [Diehn M et al. (2008) PNAS PMID: 18362333 epub ahead of print]. GMB is untreatable and most patients die within 15 months of diagnosis. At present, diagnosis and treatment is guided largely by biopsy of the tumour followed by microscopic examination of tumour cells. However this current approach has two major flaws: (1) it involves potentially dangerous brain surgery; and (2) individual tumours often behave very differently, even though their cells look similar.

 

As an alternative, GMB can also be visualised using non-invasive magnetic resonance imaging (MRI) to identify different tumour characteristics. A team of US researchers have combined MRI with gene-expression studies of individual tumours to correlate patterns of gene expression that are associated with a specific appearance on MRI scans. For example, increased activity of genes associated with hypoxia and the formation of new blood vessels (which is thought to be needed for tumour growth) is associated with a particular appearance on MRI; the authors propose that the corresponding MRI characteristics can act as a surrogate biomarker to identify which tumours might respond well to anti-angiogenic therapy (which stops the formation of new blood vessels). It is also suggested that other imaging techniques could be combined with gene mapping approaches (see news article).

 

Non-invasive testing for more common conditions such as diabetes also receives a boost with the identification of 1116 proteins that are secreted in human saliva [Denny P et al. (2008) J Proteome Res, PMID: 18361515, epub ahead of print]. The studies authors estimate that as many as 20% of the proteins present in saliva are also found in blood, including several proteins with known roles in Alzheimer’s, Huntington’s and Parkinson’s diseases as well as several cancers and diabetes. Saliva-based tests are already well established for detecting human immunodeficiency virus (HIV) and hepatitis infections. Identifying the range of saliva proteins should provide new targets for diagnosing and monitoring disease in saliva rather than blood or urine (see also associated news report).

 

These two studies outline the potential of biomolecular tests for providing potentially safer, more convenient diagnostics; a third study highlights the potential for increased sensitivity of primary screening for cervical cancer. Published in the Journal of the National Cancer Institute, this clinical trial of almost 45 000 women shows that testing for human papillomavirus (HPV) DNA in cervical cells is more effective at detecting precancerous cervical lesions than the current ‘gold standard’ of the Pap test [Ronco G et al. (2008) PMID: 18364502, epub ahead of print]. Infection with HPV accounts for virtually all cases of cervical cancer. The HPV test identified almost twice as many women with premalignant lesions requiring treatment than conventional testing in women in the 35-60 age group. Furthermore, it does not increase the incidence of false-positives (i.e. women who test positive, but do not have such lesions) in this age group. DNA-based testing also identifies more potential cases in younger women (25-34 years), although it appears that a significant number of these infections are likely to resolve naturally. Because of this the authors propose that it is more appropriate to rescreen younger women 12 months after the initial DNA test rather than refer them directly for further investigation.

 

These examples give some idea of the breadth of the possible impact of genomic applications in clinical medicine within the next few years. With the increasing number of large, high-powered studies to identify disease-gene associations and potential avenues for therapeutic development, it is easy to loose sight of the better-advanced potential for genomic medicine in other areas, such as diagnostic and/or prognostic testing and screening programmes.