Category Archives: Genetic Medicine

May 11, 2012

Connie K. Ho for RedOrbit.com

Researchers at Loyola University Chicagos Stritch School of Medicine have found that patients see both benefits and risks from direct-to-consumer genetic tests. Dr. Katherine Wasson, a specialist on the ethics of direct-to-consumer genetic tests, and colleagues conducted the experiment. The study, published in the American Journal of Bioethics Primary Research, showed that the patients were concerned about the end game of the genetic test results.

There are a few companies, such as 23andMe, deCODE Genetics and Navigenics, that currently test consumers for single gene disorders like cystic fibrosis; complex disorders with multiple genes like cancer, heart disease, and diabetes; traits like hair color, eye color, and baldness; as well as allergies to drugs like Coumadin for a fee ranging from $100 to $1,500. Normally, consumers can order these tests directly and receive the exams without having to go through a health-care professional like a geneticist or a genetic counselor.

In the study, the researchers conducted four focus groups with 29 participants who were primary care patients at Loyola University Medical Center. After they received information about the direct-to-consumer genetic testing, they were to give their opinions on the exams. The focus groups lasted about an hour and a half to two hours, with much of the answers being recorded and transcribed. Following the focus groups, researchers read and analyzed transcripts of the sessions and looked for themes that came out from the data.

Even though direct-to-consumer genetic tests werent covered under insurance, many of the participants were willing to pay the $10 to $20 price and a few of them were willing to pay up to $100 to $400.

This situation could exacerbate inequalities in the health-care system, with those having greater financial resources being able to access this elective health-related information while those with fewer resources are unable to pay for it, noted the researchers in the report.

Participants in the focus groups also stated that they were interested in having their children tested, including those who were adopted or were from foster homes. They believed that the tests would provide useful information for the future. However, this perspective is not shared by medical professionals who recommend that children should only be tested if theres a disease to be investigated; otherwise, children should wait until they are adults to be tested.

Children could be tested without understanding its implications, and parents might take actions that are inappropriate and potentially harmful, based on results without consulting a qualified health professional, explained the researchers in the article.

The researchers also found that there were four main reasons participants were involved in the study. In particular, they hoped to gain more information, seek prevention, seek intervention, and to help others. They also mentioned concerns about testing, including questions regarding the accuracy of the tests, the interpretation of the exams, the ethical issues raised with the tests, as well as the ability to share the testing information with consumers physicians.

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Focus Groups Share Thoughts on Direct-To-Consumer Genetic Tests

Scientists have uncovered genetic signs that could help doctors predict how breast cancer patients will respond to chemotherapy.

Researchers led by McMaster University biochemist John A. Hassell found two sets of genes that could indicate the presence of higher levels of two proteins targeted by commonly used chemotherapy drugs.

They reported their results in a paper published Thursday in the journal BMC Medical Genomics.

Hassell and his colleagues focused on the enzyme TOP2A or the protein beta-tubulin, which are targeted by anthracycline and taxane chemotherapy drugs, respectively. Without those targets, the chemotherapy won't work.

The researchers built their 'gene expression signatures' by looking at the expression levels - how often the genes are transcribed - of genes that correlated with the expression levels for the genes encoding TOP2A and beta-tubulin.

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If the signature indicates a patient's tumor is making a lot of TOP2A and beta-tubulin, there's a good chance that chemotherapy will be more effective. And on the flip side, if a patient's genetic signature indicates that chemotherapy wouldn't be as successful, doctors can avoid giving the patient a treatment that would do more harm than good.

Using data for a group of 488 breast cancer patients, Hassell and his team found they could use these genetic signatures to accurately predict if anthrocycline or taxane drugs had successfully obliterate a patient's cancer.

"This is all in the realm of personalized medicine," Hassell said in a telephone interview.

Hopefully, finding these kinds of genetic indicators will mean that eventually a breast cancer patient can be treated with a chemotherapeutic agent tailored to her particular type of breast cancer, according to Hassell.

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Genetic ‘Signature’ Predicts Breast Cancer Chemotherapy Response: Study

Public release date: 11-May-2012 [ | E-mail | Share ]

Contact: Dianne G. Shaw dgs@med.unc.edu 919-966-7834 University of North Carolina School of Medicine

Cancer therapies targeting specific molecular subtypes of the disease allow physicians to tailor treatment to a patient's individual molecular profile. But scientists are finding that in many types of cancer the molecular subtypes are more varied than previously thought and contain further genetic alterations that can affect a patient's response to therapy.

A UNC-led team of scientists has shown for the first time that lung cancer molecular subtypes correlate with distinct genetic alterations and with patient response to therapy. These findings in pre-clinical models and patient tumor samples build on their previous report of three molecular subtypes of non-small cell lung cancer and refines their molecular analysis of tumors.

Their findings were published in the May 10, 2012 online edition of the Public Library of Science One.

Study senior author, Neil Hayes, MD, MPH, associate professor of medicine, says, "It has been known for about a decade of using gene expression arrays that "molecular subtypes" exist. These subtypes have molecular "fingerprints" and frequently have different clinical outcomes. However, the underlying etiologies of the subtypes have not been recognized. Why do tumors form subtypes?

"Our study shows that tumor subtypes have different underlying alterations of DNA as part of the difference. These differences are further evidence of the importance of subtypes and the way we will use them. For example, the mutations are different which may imply much more ability to target than previously recognized. Also, we are starting to get a suggestion that these subtypes may reflect different cells of origin that rely on different cancer pathways. This is further unlocking the diversity of this complex disease." Hayes is a member of UNC Lineberger Comprehensive Cancer Center.

The team first defined and reported in 2006 on three lung cancer molecular subtypes, named according to their genetic pattern bronchoid, squamoid and magnoid.

In this PLoS One paper they sought to determine if distinct genetic mutations co-occur with each specific molecular subtypes. They found that specific genetic mutations were associated with each subtype and that these mutations may have independent predictive value for therapeutic response.

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Molecular subtypes and genetic alterations may determine response to lung cancer therapy

07-05-2012 12:34 Autism, just like any chronic health condition, is the result of genetic predispositions interacting with modifiable environmental factors. The key is to identify the contributing factors in each case. Some of the common factors include nutrient insufficiencies, toxin exposure, food allergies, intestinal yeast overgrowth, infections, and more. New functional medicine laboratory tests help to tailor the treatment in each case of autistic spectrum disorder. Personalized treatment based on this type of evaluation helps many patients with autism improve to varying degrees, sometimes a great deal. By Dr. Joseph Debé, Board Certified Nutritionist • • (516) 829-1515 Register for upcoming webinars at

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Autism - A Functional Medicine Approach to Treatment- a webinar presented on 12-15-2010 - Video

ScienceDaily (May 7, 2012) The cells that slough off from a cancerous tumor into the bloodstream are a genetically diverse bunch, Stanford University School of Medicine researchers have found. Some have genes turned on that give them the potential to lodge themselves in new places, helping a cancer spread between organs. Others have completely different patterns of gene expression and might be more benign, or less likely to survive in a new tissue. Some cells may even express genes that could predict their response to a specific therapy. Even within one patient, the tumor cells that make it into circulating blood vary drastically.

The finding underscores how multiple types of treatment may be required to cure what appears outwardly as a single type of cancer, the researchers say. And it hints that the current cell-line models of human cancers, which showed patterns that differed from the tumor cells shed from human patients, need to be improved upon.

The new study, published May 7 in PLoS ONE, is the first to look at so-called circulating tumor cells one by one, rather than taking the average of many of the cells. And it's the first to show the extent of the genetic differences between such cells.

"Within a single blood draw from a single patient, we're seeing heterogeneous populations of circulating tumor cells," said senior study author Stefanie Jeffrey, MD, professor of surgery and chief of surgical oncology research.

For over a century, scientists have known that circulating tumor cells, or CTCs, are shed from tumors and move through the bloodstreams of cancer patients. And over the past five years, there's been a growing sense among many cancer researchers that these cells -- accessible by a quick blood draw -- could be the key to tracking tumors non-invasively. But separating CTCs from blood cells is hard; there can be as few as one or two CTCs in every milliliter of a person's blood, mixed among billions of other blood cells.

To make their latest discovery, Jeffrey, along with an interdisciplinary team of engineers, quantitative biologists, genome scientists and clinicians, relied on a technology they developed in 2008. Called the MagSweeper, it's a device that lets them isolate live CTCs with very high purity from patient blood samples, based on the presence of a particular protein -- EpCAM -- that's on the surface of cancer cells but not healthy blood cells.

With the goal of studying CTCs from breast cancer patients, the team first tested whether they could accurately detect the expression levels of 95 different genes in single cells from seven different cell-line models of breast cancer -- a proof of principle since they already knew the genetics of these tumors. These included four cell lines generally used by breast cancer researchers and pharmaceutical scientists worldwide and three cell lines specially generated from patients' primary tumors.

"Most researchers look at just a few genes or proteins at a time in CTCs, usually by adding fluorescent antibodies to their samples consisting of many cells," said Jeffrey. "We wanted to measure the expression of 95 genes at once and didn't want to pool our cells together, so that we could detect differences between individual tumor cells."

So once Jeffrey and her collaborators isolated CTCs using the MagSweeper, they turned to a different kind of technology: real-time PCR microfluidic chips, invented by a Stanford collaborator, Stephen Quake, PhD, professor of bioengineering. They purified genetic material from each CTC and used the high-throughput technology to measure the levels of all 95 genes at once. The results on the cell-line-derived cells were a success; the genes in the CTCs reflected the known properties of the cell-line models. So the team moved on to testing the 95 genes in CTCs from 50 human breast cancer patients -- 30 with cancer that had spread to other organs, 20 with only primary breast tumors.

"In the patients, we ended up with a subset of 31 genes that were most dominantly expressed," said Jeffrey. "And by looking at levels of those genes, we could see at least two distinct groups of circulating tumors cells." Depending on which genes they used to divide the CTCs into groups, there were as many as five groups, she said, each with different combinations of genes turned on and off. And if they'd chosen genes other than the 95 they'd picked, they likely would have seen different patterns of grouping. However, because the same individual CTCs tended to group together in multiple different analyses, these cells likely represent different types of spreading cancer cells.

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Not all tumor cells are equal: Huge genetic diversity found in cells shed by tumors

Michael Pacanowski, PharmD, MPH; Shashi Amur, PhD; Issam Zineh, PharmD, MPH Author Affiliations: Genomics Group, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.

Treatment of chronic hepatitis C (CHC) is a prototype for personalized medicine. Combination therapy with peginterferon alfa plus ribavirin was the standard of care for more than a decade. Greater understanding of the disease and determinants of treatment response have improved sustained virologic response (SVR) rates from less than 10% with interferon alfa in the 1990s to more than 80% with contemporary triple therapy regimens that include direct acting antivirals (DAAs) (Figure). Patient-specific factors such as viral genotype and early on-treatment responses are considered in therapeutic individualization. New approaches to search the human genome for predictors of drug response led to the discovery that single-nucleotide polymorphisms (SNPs) near the host IL28B gene are among the strongest predictors of response to peginterferon alfa and ribavirin. This Viewpoint discusses the evolution of CHC pharmacogenetics, its real-time incorporation into recent regulatory science evaluations, and its application in future drug development.

cDNA indicates complementary

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New Genetic Discoveries and Treatment for Hepatitis C [Viewpoint]