Category Archives: Research


The Human Genome Project, ENCODE and Cancer Care

Genomics in Oncology

A newly diagnosed cancer patient and their family might have barely moved from the first stage to the next of the five stages of grief but, regardless of the course of their emotional journey, their cancer vocabulary begins to grow from day one. Biopsy, staging, chemo, neutropenia,… words that had meant nothing to them before, take on a very tangible meaning invoking thoughts of hospital beds and days spent being sick. As the battle with cancer continuous, their vocabulary continues to evolve as well. Remission, transplant, … relapse, metastasis, morphine, …hospice; relief alternating with despair, a roller coaster ride with too many ups and downs.

In the last few years, a newer set of words  are beginning to make their way into the cancer lexicon- whole genome sequencing (WGS), targeted therapies, biomarkers… words that are becoming associated with some recent successes and cautious optimism as we relentlessly search for a cure to cancer. These partial successes, the understanding that cancer is a genetic disease, and the decreasing cost of whole genome sequencing raise important questions about making tumor sequencing an integral part of cancer treatment.

Central to this discussion are several different scientific and social issues. On the scientific side, intratumor heterogeneity, challenges with data interpretation and management, and physician training in genomics dominate the conversation. In the social area, cost and insurance coverage, and ethical issues remain center stage.

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One genome at a time: Mapping the cancer battlefield

Patients and families turn to genomic medicine to treat cancer

Most of us probably associate being sick with the entire body- a fever, aches, chills and other broad symptoms. When it comes to a disease like cancer, we might take an organizational step or two down to think of a specific organ or tissue: breast, lung or brain cancer.

But increasingly, patient’s stories point clearly toward a finer resolution of cancer diagnosis, down to the level of a single gene. A report in the New York Times last week describes how a team of researchers worked to identify the genetic aberration underlying a colleague’s cancer, and helped treat his leukemia with an off-label drug currently used to treat kidney cancers.

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Exome sequencing pins down unusual suspects

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…

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Travel Grants Spring 2012 winner: Catarina Correia

And finally, a big round of applause for our first place travel grant winner, Dr. Catarina Correia! She researches protein interaction networks in autism spectrum disorders and presented her recent results at the International Meeting for Autism Research in Toronto, ON last month. We’re glad the travel grant helped her attend!  

I am currently pursuing a post-doctoral project at Instituto Gulbenkian de Ciência and Instituto Nacional de Saúde Dr. Ricardo Jorge (Portugal) working on the analysis of GWAS carried out by the Autism Genome Project (AGP), a large international consortium for autism genetics. My research aims to develop a network-based approach for GWAS data analysis by combining association results with protein-protein interaction data, and characterize potentially pathogenic CNVs identified in the AGP whole genome CNV analysis.  Read more…

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Travel Grants Spring 2012 winner: Malay Bhattacharyya

Congratulations to our second travel grant winner! Read on to find out how he uses NextBio Research to explore oncogenic microRNAs.In Malay’s words: 

I become truly amazed when I look back on my career and see how a student with undergraduate degrees in Computer Science and Electronics turned into a biology researcher. In the very first week of graduate school, I received an article on microRNAs (miRNAs), a class of short non-coding regulators of protein-coding genes, from my supervisor. Ever since that first read, I have been hooked on these endogeneous RNAs for four years and counting.  Read more…

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Chromatin clustering may hold cancer clues

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…

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Shedding light on genomic signatures of melanoma

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…

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Finding MARS mutants in the human exome

Talks at the Sanford-Burnham Rare Disease Day Symposium highlight the “transformative potential of exome sequencing” for rare Mendelian diseases

Individually rare yet collectively common, ‘orphan’ or rare diseases affect nearly 30 million Americans every year. Despite the current explosion in genomic data and personalized medicine strategies, little is known about what causes these rare genetic disorders, how they progress or options for treatment. Marking Rare Disease Day, a one-day symposium at the Sanford Burnham Medical Research Institute in La Jolla, CA featured talks by several researchers studying disorders of glycosylation, especially in children. Several of these discussions highlighted how studying rare conditions can enhance the ways we detect, diagnose or research relatively more common diseases. Read more…

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Epigenetic changes mark up ovarian cancer cells

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…

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Tumor suppressor or oncogene? The argument continues…

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…

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