Category Archives: Gene Medicine

ClinGen is funded by the National Human Genome Research Institute (NHGRI), which is itself part of the National Institutes of Health. Erin Ramos, PhD, a project scientist for ClinGen and program director for the division of genomic medicine at NHGRI, said in a release that NHGRI developed ClinGen as a way to standardize guidelines for genetic testing. A panel of experts, including researchers, clinicians and genetic counselors comb through scientific evidence from research papers to identify gene-disease relationships as either definitive, strong, moderate, limited, disputed or refuted.

The experts reported that three genesKCNQ1, KCNH2 and SCN5Awere indeed backed by enough evidence to be categorized as definitive genetic triggers for long QT syndrome. They classified four other genes as either strong or definitive for causing atypical forms of long QT syndrome, but the panel didnt find enough evidence to support the remaining 10 genes.

Those 10 genes were all placed in either the limited or disputed category for their link to long QT syndrome, and for that reason the authors said they dont recommend using them as markers in routine clinical tests.

Our study highlights the need to take a step back and to critically evaluate the level of evidence for all reported gene-disease associations, especially when applying genetic testing for diagnostic purposes in our patients, Gollob said in a statement. Testing genes with insufficient evidence to support disease causation only creates a risk of inappropriately interpreting the genetic information and leading to patient harm.

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Experts dispute 9 of 17 genes once linked to long QT syndrome - Cardiovascular Business

Today is World Cancer Day a day for raising the voices of cancer survivors, loved ones, and the people who are working endlessly to find solutions. This years theme is I am and I will: a recognition of the power each individual has to make an impact.

Each year, PLOS ONE publishes more than 1000 new research articles in cancer and oncology from authors who have dedicated their careers to studying this disease. In celebration of this years theme, were sharing their stories which inspired the science we use to understand and fight this disease.

My research group is mainly focused on the study of lung and pancreatic cancers, which are associated with high morbidity and mortality rates, worldwide. We use high throughput methods to identify new biomarkers and regulatory pathways and functional assays to improve our understanding of disease biology.

Patricia Pintor dos Reis, Faculty of Medicine, So Paulo State University UNESP Botucatu, SP, BRAZIL.

MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma.Tainara F. Felix, Rainer M. Lopez Lapa, Mrcio de Carvalho, Natlia Bertoni, Tomas Tokar, Rogrio A. Oliveira, et al

Bioinformatics is my tool and cancer research is my subject. My dad and many other people died of cancer and I want to uncover what causes cancer. And I love math and computers, which attracted me to become a bioinformatician. Now I am working for NCI initiative Ras program at Frederick National Lab for Cancer Research, which tries to tackle the most critical and ancient gene in cancer biology: Ras genes.

My last paper on PLOS ONE is about common pitfalls often seen in the survival analysis in the field. We wish to first alert researchers about the pitfalls when they perform survival analysis and to provided a novel method that shall help avoid the pitfalls.

Ming Yi, NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, United States of America

GradientScanSurvAn exhaustive association test method for gene expression data with censored survival outcome.Ming Yi, Ruoqing Zhu, Robert M. Stephens

The goal of my research is to develop an agent that promotes apoptosis in cancer cells but not in normal cells. To accomplish this goal, I explored different protein targets and pathways that included but are not limited to matrix type-I metalloprotease I (MT1-MMP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and oxidative stress.

Dmitri Rozanov, Department of Molecular and Medical Genetics, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, United States of America

Targeting mitochondria in cancer therapy could provide a basis for the selective anti-cancer activity.Dmitri Rozanov, Anton Cheltsov, Aaron Nilsen, Christopher Boniface, Isaac Forquer, et al

I focus on H&N/Skull base cancers and mechanisms of treatment resistance within HPV positive and negative cancers. Understanding mechanism of treatment resistance will enable us to target new pathways for improving patient outcomes.

Dukagjin Blakaj, The James Cancer Center, Ohio State University, Columbus, OH, United States of America

Association of an intact E2 gene with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome in HPV16 positive head and neck squamous cell carcinoma.Nicole V. Anayannis, Nicolas F. Schlecht, Miriam Ben-Dayan, Richard V. Smith, Thomas J. Belbin, et al

My particular area of research is the staging of colon cancer, it is important because colon cancer is a top 3 killer (of all cancer types) and we need new treatment strategies. However without accurate staging (i.e. determining how advanced the tumor is), it is nearly impossible to develop these new strategies.

Elias Nerad, The Netherlands Cancer Institute, Amsterdam The Netherlands.

The Apparent Diffusion Coefficient (ADC) is a useful biomarker in predicting metastatic colon cancer using the ADC-value of the primary tumor.Elias Nerad, Andrea Delli Pizzi, Doenja M. J. Lambregts, Monique Maas, Sharan Wadhwani, et al

I have always wanted to understand the incredible organization of brain functions and how to cure patients with brain lesions. My research field focuses on brain anatomy, brain functions, neuroimaging and how all these aspects together can improve the treatment of patients with cerebral tumors. My work tried to change the standard topographical classification of brain tumors to a model including more detailed information regarding the tumor infiltration along the white matter fibers.

This model perfectly fits the open access principle because it is not based on expensive technology, rather on a basic idea merging anatomy neuroimaging and oncology. I believe that anyone in the world can reproduce this classification method with standard MRI pictures contributing to a more extensive and shared knowledge in this field.

Francesco Latini, Department of Neuroscience, Neurosurgery, Uppsala University, Uppsala, Sweden

A novel radiological classification system for cerebral gliomas: The Brain-Grid.Francesco Latini, Markus Fahlstrm, Shala G. Berntsson, Elna-Marie Larsson, Anja Smits, Mats Ryttlefors

Find out more about the causes of cancer and interventions to prevent and manage the disease in the PLOS Cancer Research Special Collection.

PLOS ONE will also be launching a Call for Papers for Cancer Metastasis research and invites submissions that report on the biochemical and cell biological basis of metastasis, including but not limited to cell adhesion, cell migration, cytoskeletal dynamics, cell polarity, tumour heterogeneity, tumour dormancy and the tumour microenvironment.

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Meet the PLOS ONE Cancer and Oncology Authors - PLoS Blogs

We have all heard of the term gene and DNA, but little do we know about the impact of changes in them known commonly as genetic mutations. Most cancers are associated with these changes in specific genes which are sub-units of the genetic material, DNA. In this era of modern medicine & treatment, certain genetic mutations have been identified to be responsible for several diseases including cancer and targeting such mutations play a major role in the overall management of the disease, to improve the quality of the life and cure.

In the past two decades, there has been an increasing number of cancer cases in India. According to the Globocan 2018 data, about 1.16 million new cancer cases in India were reported with close to 7.9 lakh deaths. In India, the cancer subtypes in descending order are breast cancer (14 percent), lip/oral cavity cancers (10.4 percent), cervical cancer (8.4 percent), lung cancer (5.9 percent) and stomach cancer (5 percent) followed by others.

Most cancers are associated with changes in specific genes which are sub-units of the genetic material DNA.

The question that arises that How genetic testing would help in understanding genetic mutation and its relation to cancer/s? The simple answer to this question is, whatever one asks for. Genetic testing provides varied answers, starting from predisposition, and events before onset of cancer to treatment planning and monitoring as well as detection of early relapse/recurrence.

How can the genetic information related to cancer, be decoded even before the cancer onset? Well, the presence of certain gene mutations increases the chances of developing cancers drastically. These cancers are known as hereditary cancers, and the process is known as hereditary risk assessment. Understanding genetic mutations can help one understand whether there are increased chances of developing cancer. For example, any woman is at a 12 percent lifetime risk of developing breast cancer, in general population, but if there is a presence of harmful BRCA1 mutation, in a given individual due to inheritance, this risk can go as high as 70 percent.

Once cancer has developed, there are various ways in which these genetics tests can prove handy. Understanding genetic mutations can help the oncologist diagnose and differentially diagnose cancer subtypes in a more informed manner. Further certain genetic mutations help in understanding if the cancer progression will be aggressive or not. For example, in case of a leukaemia subtype: chronic lymphocytic leukaemia (CLL), the presence of IGHV gene mutation indicates that cancer wont progress aggressively. In medical terms it is known as good prognosis. On the other hand, there are some gene mutations that indicate poor prognosis of cancer as well.

Coming to the most known of application of genetic testing, we all have heard of what is called targeted treatment. Presence of certain gene mutations help the oncologists target the cancer as far as treatment is concerned. For example, in lung cancer, there are various classes of drugs that are based on gene mutations, such as EGFR inhibitors, which have a better effect on EGFR mutated lung cancers.

Certain genetic mutations help in understanding if the cancer progression will be aggressive or not.

Other applications of genetic testing include assessment of the treatment response for a given drug, also to detect the early recurrence in a periodic manner by a non-invasive procedure to check for cancer-specific mutations in the plasma of the blood sample, also known as liquid biopsy testing

Like all other subjects, cancer genetics is also something where India has certain unique features. There are multiple research papers that mention that in lung cancer, the prevalence of EGFR mutations is higher in south-Asian, particularly Indian population, as compared to the western populations. This provides an added advantage of treating these patients with targeted therapy for killing the specific cancer cells, thus avoiding the side effects associated with conventional chemotherapy. Hence understanding the mutation status of EGFR gene becomes imperative in case of lung cancers.

Similarly, there is a subclass of breast cancer called triple-negative breast cancers (TNBC), where there is an absence of receptors known to fuel breast cancer growth- Estrogen, Progesterone and Her-2/Neu gene. This is one of the most aggressive subtypes of breast cancer, where there are to targeted therapies available so far, and the standard of care remains conventional chemo-radiotherapy/surgery. Considering its aggressive behaviour the recurrence rates are very high in this subtype of cancers, and nearly 20 percent of these women are BRCA1/BRCA2 mutation carriers. As far as India is concerned, the triple-negative breast cancers incidence is higher in India (30 percent) as compared to the western population (12-17 percent), and have a poorer prognosis and survival (60 percent: 5 years age-adjusted survival) as compared to the Caucasian population (80 percent: 5 year age adjusted survival).

Talking about BRCA1 mutated breast cancers, one particular mutation, DelAG, is considered to be founder mutation in Ashkenazi Jewish community. Founder mutations is when a genetic alteration is observed with high frequency in a group that is or was geographically or culturally isolated, in which one or more of the ancestors was a carrier of the altered gene. In our experience, we have seen this founder mutation in Indian sub-population as well over and above Ashkenazi Jewish community.

In conclusion, genetic testing is aimed at providing clarity and insights about a persons cancer to the Oncologists that helps them make an informed decision. An increasing number of Oncologists have adopted genetic testing as an important tool for diagnosis and treatment planning of cancer and its management. Our constant effort is aimed to ensure, maximum number of cancer patients get benefitted by this technology in the society.

Dr Vidya Veldore is a principal scientist for Oncology at MedGenome Labs Ltd.

Updated Date: Feb 04, 2020 17:32:40 IST

Tags :Cancer,Cancer Day. World Cancer Day 2019,Cancer Patients,Diagnosis Of Cancer,DNA,Gene Mutations,Genes,Genetics Of Cancer,Genetics Tests,Oncologists,Oncology,Types Of Cancer,World Cancer Day

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World Cancer Day: Going back to the basics The genetics of cancer - Firstpost

MEDFORD/SOMERVILLE, Mass. (February 4, 2020)Researchers led by biologists at Tufts University have discovered that the brains of developing embryos provide signals to a nascent immune system that help it ward off infections and significantly improve the embryos ability to survive a bacterial challenge. Using frog embryos, which continue to develop with their brains removed, the researchers found that embryos without a brain are not able to marshall the forces of immune cells to an injury or infection site, leading the embryo to succumb to an infection more quickly. By contrast, the presence of a brain crucially helps direct immune cells to the site of injury to overcome the bacterial threat. The study was published today in NPJ Regenerative Medicine.

In a developing embryo, both brain and immune system are not fully formed. The immune system, for its part, consists mostly of an innate system of cells that respond immediately to infection and do not require training or produce antibodies. Nevertheless, these cells require signals that prompt them to move toward an infection site and trigger a response.

The research team found that the brain appears to contribute to the signals that guide the nascent immune system. When brainless frog embryos were infected with E. coli, only about 16% of embryos survived, while the presence of a brain protected more than 50% from the infection. By following markers of immune cells, researchers confirmed that the effect is not due to the missing brain somehow hampering immune system development because the composition of the immune cells remained the same with or without a brain. Instead, they found that the effect was due to the brain sending signals to the immune cells to move toward the site of an infection.

We found that macrophages innate immune system cells that can swallow up bacteria and destroy them to reduce the burden of an infection do not migrate appropriately without the presence of the brain said Michael Levin, Vannevar Bush Professor of Biology at Tufts Universitys School or Arts and Sciences and Associate Faculty at Harvards Wyss Institute, director of the Allen Discovery Center at Tufts and corresponding author of the study. Without the brain and its neurotransmitter signals, gene expression and innate immune system activity go awry, resulting in increased susceptibility to bacterial pathogens.

Other roles for the embryonic brain signaling during infection may include inducing cellular responses, for example preventing cell death or reducing inflammation, that help protect against the harmful effects of the infection.

Immune system abberations were also observed in brainless embryos that were further developed. When the researchers tracked myeloid cells, a class of immune cells that includes macrophages, neutrophils and others, after an injury, they found that the myeloid cells in brainless embryos gathered in locations far from the injury site. By contrast, myeloid cells in normal embryos with intact brains would pile up at the injury site to assist in healing. In fact, in the brainless embryo, the myeloid cells tended to cluster around abnormal, disorganized peripheral nerve networks, also a by-product of brain absence, as demonstrated in earlier studies.

An examination of aberrations in genetic expression in brainless embryos also pointed to the reduction of the neurotransmitter dopamine (a signaling chemical used in the brain for learning and motivation), and that dopamine may play a role in activating immune cells to migrate in the early stages of an infection. The absence of an immune cell quorum at the infection site leads the brainless embryos to become more susectible to its lethal effects.

Our results demonstrate the deep interconnections within the bacteria-brain-body axis: the early brain is able to sense the pathogenic bacteria and to elaborate a response targeted to fight against the cellular and molecular consequences of the infection, said Celia Herrera Rincon, Research Scientist II at the Allen Discovery Center at Tufts, and first author of the study.

Other authors of this study include: Jean-Francois Par, Christina Harrison, Alina Fischer, and Sophia Jannetty at the Allen Discovery Center at Tufts; Christopher Martyniuk, associate professor in the Department of Physiological Sciences at University of Florida; and Alexandre Dinis and Vishal Keshari, graduate students, and Richard Novak, senior staff engineer at the Wyss Institute for Biologically Inspired Engineering, Harvard Universiy.

This research was supported by the Templeton World Charity Foundation Independent Research Fellowship (TWCF0241) and the Allen Discovery Center program through The Paul G. Allen Frontiers Group (12171), as well as The Defense Advanced Research Projects Agency(DARPA, W911NF-16-C-0050), and the National Institutes of Health (AR055993, AR061988). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Herrera-Rincon, C., Par, J-F, Martyniuk, C.J., Jannetty, S.K., Harrison, C., Fischer, A., Dinis, A., Keshari, V., Novak, R., and Levin, M. An in vivo brainbacteria interface:

the developing brain as a key regulator of innate immunity. NPJ Regenerative Medicine (31 Jan 2020) DOI: 10.1038/s41536-020-0087-2

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About Tufts University

Tufts University, located on campuses in Boston, Medford/Somerville and Grafton, Massachusetts, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.

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Brain links to embryonic immunity, guiding response of the troops that battle infections - Tufts Now

Researchers at KU Leuven have discovered that a defect in the ATP13A2 gene causes cell death by disrupting the cellular transport of polyamines. When this happens in the part of the brain that controls body movement, it can lead to Parkinsons disease.

With more than six million patients around the world, Parkinsons disease is one of the most common neurodegenerative disorders. Around twenty genetic defects have already been linked to the disease, but for several of these genes, we dont know what function they fulfill. The ATP13A2 gene used to be one of these genes, but researchers at KU Leuven have now discovered its function in the cell. The researchers explain how a defect in the gene can cause Parkinsons disease in their article ATP13A2 deficiency disrupts lysosomal polyamine export published in Nature.

We found that ATP13A2 transports polyamines and is crucial for their uptake into the cell, explains senior author Peter Vangheluwe, PhD, from the Laboratory of Cellular Transport Systems. Polyamines are essential molecules that support many cell functions and protect cells in stress conditions. But how polyamines are taken up and transported in human cells was still a mystery. Our study reveals that ATP13A2 plays a vital role in that process. Our experiments showed that polyamines enter the cell via lysosomes and that ATP13A2 transfers polyamines from the lysosome to the cell interior. This transport process is essential for lysosomes to function properly as the waste disposal system of the cell where obsolete cell material is broken down and recycled. However, mutations in the ATP13A2 gene disrupt this transport process, so that polyamines build up in lysosomes. As a result, the lysosomes swell and eventually burst, causing the cells to die. When this happens in the part of the brain that controls body movement, this process may trigger the motion problems and tremors related to Parkinsons disease.

Unraveling the role of ATP13A2 is an important step forward in Parkinsons research and sheds new light on what causes the disease, but a lot of work remains to be done.

Vangheluwe continues: We now have to investigate how deficient polyamine transport is linked to other defects in Parkinsons disease such as the accumulation of plaques in the brain and malfunctioning of the mitochondria, the energy factories of the cell. We need to examine how these mechanisms influence each other, he says. The discovery of the polyamine transport system in animals has implications beyond Parkinsons disease as well, because polyamine transporters also play a role in other age-related conditions, including cancer, cardiovascular diseases, and several neurological disorders. Now that we have unraveled the role of ATP13A2, we can start searching for molecules that influence its function. Our lab is already collaborating with the Centre for Drug Design and Discoverya tech transfer platform established by KU Leuven and the European Investment Fundand receives support from the Michael J. Fox Foundation.

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Function of Gene Implicated in Parkinson's Disease Discovered - Clinical OMICs News

BOSTON--(BUSINESS WIRE)--Decibel Therapeutics, a development-stage biotechnology company developing novel therapeutics for hearing loss and balance disorders, today announced a new strategic research focus on regenerative medicine approaches for the inner ear. The company is also announcing a collaboration and option agreement that gives Decibel exclusive access to novel compounds targeting proteins in a critical regenerative pathway.

Decibels research focus on regeneration will be powered by the companys research and translation platform. The company has built one of the most sophisticated single cell genomics and bioinformatics platforms in the industry to identify and validate targets. Decibel has also developed unique insights into regulatory pathways and inner ear delivery mechanisms that together enable precise control over gene expression in the inner ear and differentiate its AAV-based gene therapy programs.

Our deep understanding of the biology of the inner ear and our advanced technological capabilities come together to create a powerful platform for regenerative medicine therapies for hearing and balance disorders, said Laurence Reid, Ph.D., acting CEO of Decibel. We see an exciting opportunity to leverage this platform to address a broad range of hearing and balance disorders that severely compromise quality of life for hundreds of millions of people around the world.

The first program in Decibels regeneration portfolio aims to restore balance function using an AAV-based gene therapy (DB-201), which utilizes a cell-specific promoter to selectively deliver a regeneration-promoting gene to target cells. In collaboration with Regeneron Pharmaceuticals, Decibel will initially evaluate DB-201 as a treatment for bilateral vestibulopathy, a debilitating condition that significantly impairs balance, mobility, and stability of vision. Ultimately, this program may have applicability in a broad range of age-related balance disorders. There are currently no approved medicines to restore balance. Decibel expects to initiate IND-enabling experiments for this program in the first half of 2020.

Decibel is also pursuing novel targets for the regeneration of critical cells in both the vestibule and cochlea of the inner ear; these targets may be addressable by gene therapy or other therapeutic modalities. As a key component of that program, Decibel today announced an exclusive worldwide option agreement with The Rockefeller University, which has discovered a novel series of small-molecule LATS inhibitors. LATS kinases are a core component of the Hippo signaling pathway, which plays a key role in regulating both tissue regeneration and the proliferation of cells in the inner ear that are crucial to hearing and balance. The agreement gives Decibel an exclusive option to license this series of compounds across all therapeutic areas.

The agreement also establishes a research collaboration between Decibel and A. James Hudspeth, M.D., Ph.D., the F.M. Kirby Professor at The Rockefeller University and the director of the F.M. Kirby Center for Sensory Neuroscience. Dr. Hudspeth is a world-renowned neuroscientist, a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and a Howard Hughes Medical Institute investigator. Dr. Hudspeth has been the recipient of numerous prestigious awards, including the 2018 Kavli Prize in Neuroscience.

Rockefeller scientists are at the leading edge of discovery, and we are excited to see the work of Dr. Hudspeth move forward in partnership with Decibel, said Jeanne Farrell, Ph.D., associate vice president for technology advancement at The Rockefeller University. The ambitious pursuit of harnessing the power of regenerative medicine to create a new option for patients with hearing loss could transform how we address this unmet medical need in the future.

In parallel with its new research focus on regenerative strategies, Decibel will continue to advance key priority preclinical and clinical programs. DB-020, the companys clinical-stage candidate designed to prevent hearing damage in people receiving cisplatin chemotherapy, is in an ongoing Phase 1b trial. Decibel will also continue to progress DB-OTO, a gene therapy for the treatment of genetic congenital deafness, which is being developed in partnership with Regeneron Pharmaceuticals. The DB-OTO program aims to restore hearing to people born with profound hearing loss due to a mutation in the otoferlin gene and is expected to progress to clinical trials in 2021.

To support the new research focus, Decibel is restructuring its employee base and discontinuing some early-stage discovery programs.

About Decibel Therapeutics, Inc.Decibel Therapeutics, a development-stage biotechnology company, has established the worlds first comprehensive drug discovery, development, and translational research platform for hearing loss and balance disorders. Decibel is advancing a portfolio of discovery-stage programs aimed at restoring hearing and balance function to further our vision of a world in which the benefits and joys of hearing are available to all. Decibels lead therapeutic candidate, DB-020, is being investigated for the prevention of ototoxicity associated with cisplatin chemotherapy. For more information about Decibel Therapeutics, please visit decibeltx.com or follow @DecibelTx.

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Decibel Therapeutics Announces Strategic Research Focus on Regenerative Medicine for the Inner Ear - Business Wire