Category Archives: Paper Trail

Exome sequencing pins down unusual suspects

Posted on July 3, 2012 by Jyoti M.. Filed under Paper Trail, Research

Recent research shows clinical applications of exome sequences in diagnosing in neurodevelopmental diseases

When all four children in a single family began to develop hearing, speech and intellectual defects as infants, doctors performed routine medical and genetic tests to diagnose their condition. The tests revealed little, and the children were diagnosed with a recessive form of intellectual disability, with no apparent heritable cause. Intellectual disability, like most neurodevelopmental disorders, can be particularly tricky to identify because of the lack of precise diagnostic tests and difficulty of obtaining tissue biopsies. Researchers probing the genetics underlying such conditions recently sequenced the exomes of this family and over a hundred others with affected children, implicating several novel genes in the development of these disorders. Their research, published in Science Translational Medicine last month, also hints at ways to adopt exome sequencing in clinical practice. Read more…

Chromatin clustering may hold cancer clues

Posted on June 11, 2012 by Jyoti M.. Filed under Paper Trail, Research

Transcriptional regulators can change the way chromatin loops group together

Something like the image above is probably what comes to mind first when you hear ‘chromatin structure’. In reality, DNA spends only a small portion of time in these tightly coiled chromosomes. Most chromatin within cells lies in diffuse strands within nuclei. Mapping the locations of genes on these strands, scientists have found that chromatin containing more actively expressed genes tends to cluster together, as do chromatin strands containing inactive genes. Now, two recent papers show that these specific arrangements of chromatin may hold clues to developing targeted drugs for diseases like cancer. Read more…

Shedding light on genomic signatures of melanoma

Posted on May 30, 2012 by Jyoti M.. Filed under Paper Trail, Research

A new study shows different mutation classes associated with distinct melanoma sub-types

Skin cancer remains one of the most common forms of the disease in the U.S. Though melanomas account for less than 5% of all skin cancers, they cause the large majority of deaths from the disease. Some parts of the skin (like the palms and soles) develop cancers much less frequently, and the rare ‘acral melanomas’ that originate from these types of skin have less in common with other skin cancers. Read more…

Epigenetic changes mark up ovarian cancer cells

Posted on January 3, 2012 by Jyoti M.. Filed under Case Studies, Paper Trail, Research

A genome wide methylation screen finds a potential new biomarker for ovarian cancer

In the forty years since the ‘War on Cancer’ was declared, ovarian cancer is the only form of the disease where mortality rates remain unchanged, in part due to a lack of early detection tests and specific treatments. In 2011, an estimated 15,000 women in the U.S will die of ovarian cancer.

A recent study in PLoS One by Campan et al. describes the identification of a new candidate biomarker, IFFO1, in a genome-wide DNA methylation screen of blood samples from ovarian cancer patients. Less invasive than tests that require tissue samples, and chemically and biologically more stable than RNA markers for gene expression, DNA methylation changes that can be tracked in blood samples are promising biomarkers for cancer detection and treatment. Read more…

Tumor suppressor or oncogene? The argument continues…

Posted on November 14, 2011 by Jyoti M.. Filed under Paper Trail, Research

Integrated approaches identify a new tumor suppressor function for soluble EPHA7 in follicular lymphoma

Scanning the whole genome for tumor-associated mutations has the potential to reveal new drug targets or diagnostic biomarkers that could help personalize therapy for patients. However, the complex patterns of genetic disruptions in cancer frequently prevent such candidate genes from reaching clinical significance. Combining tumor genomics with functional genetic screens and experimental models can increase the pace at which genome-wide findings are translated into clinically relevant applications.

A recent paper in Cell describes the identification of a novel tumor suppressor, EPHA7, in a genome-wide screen of follicular lymphoma samples. Supporting this finding with experimental results from animal models and cancer cell lines, the researchers also demonstrated that the gene product, a soluble protein, had the potential to dramatically improve tumor clearance in mice. Read more…

SIRT2 finds a place in the family

Posted on October 18, 2011 by Jyoti M.. Filed under Paper Trail, Research

Sirtuin 2 may suppress tumor formation in mice and humans

Sirtuins are a family of proteins that have been implicated in processes ranging from aging and tumor formation to obesity and cerebral ischemia. Seven sirtuin proteins are known to exist in mammals, two of which (SIRT1 and SIRT3), are known tumor suppressor genes. The function of sirtuin 2 (SIRT2) remained unclear however, until recent research from scientists at the National Institute of Health, Vanderbilt University and the University of Texas, Dallas discovered that SIRT2 could play an important role in preventing cancer. In a paper published in Cancer Cell this week, the researchers describe the role of SIRT2 in maintaining genomic stability in cells, a function critical in aging and cancer-related processes.
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Nicer with Dicer? Not always.

Posted on October 3, 2011 by Jyoti M.. Filed under Paper Trail, Research

Increases in Dicer gene expression improve some cancers and worsen others

Some of the tiniest players on the field, microRNAs (miRNAs) are short strands of RNA that work to control gene expression in several pathways. Though they don’t encode any proteins, miRNAs regulate genes involved in embryonic growth, cell differentiation, angiogenesis and other cellular processes. They have also gained steady prominence in cancer research, with several studies connecting abnormal miRNA regulation to cancer progression and metastasis in cell lines, animal models and samples from patients.

The potential diagnostic and therapeutic value of miRNAs has also turned attention to the molecules involved in making miRNAs in cells, particularly the enzyme Dicer. A recent study by Zhihai Ma and colleagues in PLoS One reports that higher Dicer expression correlates to more advanced stages of cutaneous melanoma, characterized by increased metastatic potential, tumor mitotic index, and other stages (as defined by the American Joint Committee on Cancer) .
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Fast, feast, forget?

Posted on August 3, 2011 by Jyoti M.. Filed under Paper Trail, Research

Finding the links between type 2 diabetes and Alzheimer’s disease

Alzheimer’s disease (AD) has been called the diabetes of the brain, with good reason. Researchers have shown that the memory loss and dementia characteristic of AD is caused by molecular disturbances in the nervous system that mimic the changes in other cells in type 2 diabetes mellitus (T2DM).

Two recent papers in the journal Cell now make another connection between the two diseases (Read more about previous connections here and here). Identifying a new role for a group of enzymes called histone deacetylases (HDACs), researchers have found a molecular pathway by which class II HDACs respond to insulin and glucagon to control blood glucose levels in mice, humans, and flies.
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A guide to lung cancer hitchhikers

Posted on July 18, 2011 by Jyoti M.. Filed under Paper Trail, Research

Distinguishing driver and hitchhiker mutations for targeted chemotherapy

Cancer genomes are complex, with multiple changes in gene sequence, expression profiles and epigenetic changes to regulatory regions. Some of these changes, termed ‘driver’ mutations, are significant to tumor formation and cancer progression, while others are simply ‘hitchhikers’ of little (known) clinical relevance.

As pharmacogenomics progresses towards identifying genetic profiles for stratified medicine strategies, distinguishing driver and hitchhiker mutations becomes essential. Two recent reports from the Translational Genomics Research Institute (TGEN), presented at the 14^th World Conference on Lung Cancer, examine signaling pathways in lung cancer to identify novel treatment strategies and potential drug targets.

Two broad categories of lung cancer exist: small cell lung cancer (SCLC), causing about 15% of all lung cancers, and non-small cell lung cancer (NSCLC). Of the three sub-forms of NSCLC, adenocarcinomas are the most prevalent, accounting for more than 50% of all lung cancer cases.
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The (long and winding) road to personalized medicine

Posted on July 15, 2011 by Jyoti M.. Filed under Paper Trail, Research

The Cancer Genome Atlas maps genomic changes in ovarian adenocarcinoma

Popping an aspirin cures headaches for nearly everyone regardless of their DNA, but some drugs only work on patients with specific genetic profiles. Herceptin, for example, is effective only in breast cancer patients whose tumors over-express the HER-2 gene, and Gleevec is specifically designed to inhibit an altered enzyme form in leukemia. Several other such drugs, designed for specific gene forms or expression patterns, are currently in use. Understanding the genetic profile of complex diseases like cancer is the first step towards designing more effective therapies.
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