Posts by Andreia Cunha

Less talking and more doing: the return of secondary genomic findings to patients

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A study published today in Genome Medicine describes a framework for returning ‘secondary’ or ‘incidental’ genomic findings to patients. We take a look at what the implications of this could be, both for patients and clinical researchers.

Close your eyes and imagine for a moment you’re a patient trying to decide whether to enroll in a genome sequencing project at the hospital where you’ re receiving treatment.

As part of the enrolment process it will be explained to you that information in your genome, unrelated to your disease, that might reveal you are at risk of developing another condition could be found. The so-called ‘incidental’ or ‘secondary’ genomic findings. The following questions might cross your mind: would I like to …

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Call for papers: Genome Medicine announces a new series on Participatory Medicine

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Later this year, Genome Medicine will publish a new thematic series focusing on Participatory Medicine. This article collection will highlight how the implementation of high-throughput technologies such as genomics, transcriptomics, proteomics, and metabolomics is promoting a paradigm shift in healthcare. In this new concept of healthcare, clinician and patient are part of the same team. Patients are empowered by more available information, and take a more active and responsible role, while clinicians welcome them as knowledgeable partners in clinical practice.

The series will be launched in late 2013 and will be guest edited by Charles Auffray (European Institute for Systems Biology and Medicine, Lyon, France) and Leroy Hood (Institute for Systems Biology, Seattle, USA).

The editors are now

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Anti-TNF-alpha therapeutics in chronic inflammatory diseases – seeing in the dark

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Multiple diseases are covered by the umbrella of poorly understood etiology coupled to an exaggerated or misguided inflammatory response. At first sight, it might seem odd that conditions as different as rheumatoid arthritis and Crohn’s disease are grouped together, but a closer look reveals that although the affected tissue is different, there are actually many common pathogenic processes. A good example is the involvement of the pro-inflammatory cytokine TNF-alpha.

Monoclonal antibodies that target TNF-alpha, such as infliximab, are used in the treatment of both diseases. However, the efficacy of the treatment can vary, and some patients can undergo long periods of therapy with no observable benefit. What if it were possible to predict beforehand which patients will respond …

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In this issue of Genome Medicine: disease in the microbial jungle, a technology for target enrichment, genomics of osteoporosis and chronic lymphocytic leukemia, and more…

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The May issue of Genome Medicine features two articles that highlight the role of microbes in human health and disease as part of a recently launched thematic series on this exact topic. Charis Eng muses on the importance of maintaining a healthy microbiome to prevent disease and discusses how microbiome profiles could be used as a diagnostic tool for cancer. On a related topic, a study by Chris Boshoff and colleagues reveals that specific genetic alterations are associated with human papillomavirus (HPV) status in head and neck squamous cell carcinoma. Notably, HPV-positive tumors have more copy number alterations in the PI3 kinase pathway, which might be important for the interpretation of current …

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With a little help from your family: advances in non-invasive prenatal diagnosis

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Genome Medicine

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

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Not a mixed bag: redefining syndromes associated with ASXL gene mutations

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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. …

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Return of incidental genetic findings: guidelines for clinical trials

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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 …

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miRNA biomarkers in osteosarcoma: crossing a new bridge

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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 …

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Cystic fibrosis modifier genes: the last refuge of the complex

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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 …

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Cancer mutations: separating the wheat from the chaff

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Genome Medicine

Cancer research has invested in cancer genome sequencing with the aim of identifying somatic mutations that drive tumorigenesis. Yet, the thousands of somatic mutations identified in cancer sequencing projects have little meaning without being able to distinguish the cancer-causing “drivers” from the neutral “passengers”. Identifying the mutations with a functional impact is one approach to distinguish driver from neutral mutations for further investigation.

Genes encoding critical proteins are likely to have a lower tolerance to non-synonymous single nucleotide variants (SNVs), compared with genes encoding less essential products. However, the tools available so far to assess the functional impact of mutations would not take this different baseline tolerance into account. Nuria López-Bigas and colleagues used germline variants from the 1000 …

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