The biotechnology company Myriad Genetics holds US and European patents on the breast cancer risk genes BRCA1 and BRCA2 and sells a diagnostic test based on these. The ethics, legality and scientific validity of these patents have been extensively debated, from the courts to the blogosphere, and on April 15th 2013, this topic is back in the limelight as the Supreme Court considers a legal challenge on the case.
Many other companies also hold gene patents, and the implications and controversies are wide-ranging. For example, they touch upon basic science – whether isolated DNA fragments are found as part of normal cellular and bodily processes and thus not patentable, as recently argued by Eric Lander, or whether …
Genome Medicine has published the first in a series of articles on “Proteomic applications in medicine”, guest edited by Sabine Bahn and Paul Guest (Cambridge University). The series aims to highlight progress and challenges in using proteomic techniques in order to gain clinical insight into disease establishment, progression, diagnosis and prognosis. Genome Medicine is now accepting research or methodology article submissions for inclusion in the series.
Guest et al. describe the technological advancements allowing biomarker research to move from discovery to validation, and eventually to the clinic in an introductory Editorial to the series. The importance of studying co-morbidities, and co-development of biomarkers with drugs is discussed.
Also in this issue, Stuart Cordwell and …
Accurate prenatal diagnosis is important to guide pregnancy and birth management, therapeutic strategies, and future family planning, but invasive diagnostic techniques are associated with a risk of miscarriage. Advances in next-generation sequencing have allowed the development of methodologies for non-invasive prenatal diagnosis (NIPD) from cell-free fetal DNA circulating in maternal blood.
There has been much discussion recently regarding moving NIPD to the clinic, and so far this technology has been mainly applied to detection of sex-linked, single gene and chromosomal abnormality disorders. A successful example is the detection of aneuploidies, as discussed in a Review and Open debate previously published in Genome Medicine. By contrast, using NIPD to diagnose complex diseases or those caused by de …
Bohring-Opitz syndrome is a clinically heterogeneous developmental condition characterized by feeding difficulties, severe developmental delays, a smaller than average head circumference, and distinctive facial features and posture. It is estimated that around half of the individuals affected have de novo truncating mutations in the additional sex combs like 1 (ASXL1) gene. The ASXL gene family is composed of three evolutionarily conserved transcriptional regulators, ASXL1, ASXL2 and ASXL3 that are known to play key roles in development.
In a study recently published in Genome Medicine, and highlighted in a Nature News piece, Matthew Bainbridge and colleagues report de novo truncating mutations in the ASXL3 gene that are associated with a clinical syndrome with features partially overlapping with Bohring-Opitz. …
Head and neck cancer is the sixth most common cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) is the most frequent form. Certain subtypes of HNSCC, such as oropharyngeal carcinoma, are infected with human papillomavirus (HPV), and patients with these HPV-positive tumors have a better prognosis than patients without and respond better to chemotherapy and radiotherapy.
To understand why the HPV-positive patients do better, a team from University College London led by Stephan Beck examined the differences in methylation patterns by sequencing HPV-positive and HPV-negative samples, and the results were recently published in Genome Medicine.
As frozen HNSCC samples are hard to get hold of, the UCL team instead developed a method that …
Later this year, Genome Medicine will publish a special issue on the topic of Single cell analysis: into the clinic. This issue will highlight the rapid advances that have been made in the separation, detection and analysis of genomic and proteomic material in single cells and how this approach will inform our understanding and treatment of disease.
The publication of these articles will be coordinated with a series of commissioned reviews and opinions written by leaders in the field including:
Garry Nolan (Stanford University, US)
James Heath (California Institute of Technology, US)
Thierry Voet (KU Leuven, Belgium and Wellcome Trust Sanger Institute, UK)
Michael Speicher (Medical University of Graz, Austria).
The Editors of Genome Medicine are now accepting submissions …
The decrease in cost and increase in efficiency of genome-scale studies means we can enjoy fast-paced generation of genomic data. In the clinic, this growth has attracted a lot of attention and many randomized clinical trials are using genomic data. During the course of a particular trial, clinicians may stumble upon genetic findings that could have health implications, but which are of no interest to the investigation in progress – so called incidental findings. The return of these incidental findings to patients has important ethical and practical considerations, but the fast pace in the genomics field has not been matched by the publication of recommendations on how best to handle them.
The Genomics and Randomized Trials Network (GARNET) analyzes …
Osteosarcoma is the most common type of bone tumor, but the lack of good biomarkers to predict the outcome of standard treatment has so far prevented patient stratification and therapy evolution. Gene expression signatures, including microRNA (miRNA) profiles, have been suggested to have predictive value for the response of a tumor to chemotherapy, but the limited availability of frozen tissue samples has hindered development of signatures with prognostic value for recurrence and survival. Formalin-fixed paraffin-embedded tissue (FFPE) is the standard sample used by histopathological laboratories but it has proved very challenging to use this for reliable expression-profiling.
This problem has now been overcome by Dimitrios Spentzos and colleagues, whose study was recently published in Genome Medicine. The …
The Human Leukocyte Antigen (HLA) is the most polymorphic region of the genome, with a key role in the immunological response. In humans, HLA genes are contained within the major histocompatibility complex (MHC) locus, consisting ofmore than 200 genes located on chromosome 6. Determining individual HLA types is of critical importance in many aspects of medicine, including transplantation, where donor and recipient tissue types must be matched in order to avoid rejection.
The enormous genetic heterogeneity of this region poses significant challenges in HLA typing. Traditionally, HLA typing has been performed using either serological testing (using white blood cells), or DNA testing (extracting DNA from the white blood cells), and relies upon amplification of the …
Cystic fibrosis is a rare but lethal autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is responsible for the balance of salt versus water movement in cells, and defects in CFTR lead to thickened secretions, for example in the lungs, which cause recurrent lung infections that eventually become fatal. The most common CFTR mutation is DeltaF508, in which the protein lacks a phenylalanine (F) residue at position 508. However, patients with the DeltaF508 mutation vary considerably in the severity of the clinical manifestation of cystic fibrosis, suggesting that other genetic factors contribute to disease phenotype.
These genetic factors, so called modifier genes, remain for the most part elusive, but the teams of …