Published by
Stanford Medicine

Cancer, Genetics, Research, Stanford News, Technology

Gene panel screens for dozens of cancer-associated mutations, say Stanford researchers

Gene panel screens for dozens of cancer-associated mutations, say Stanford researchers

Stanford scientists have shown that it’s possible to simultaneously screen for dozens of cancer-associated mutations from a single blood sample using a multiple-gene panel. The research is published today in the Journal of Clinical Oncology (subscription required).

As I describe in my release:

Gene panels allow researchers to learn the sequences of several genes simultaneously from a single blood sample. It stands to reason that screening for mutations in just a few select genes is quicker, easier and cheaper than whole-genome sequencing. The technique usually focuses on fewer than 100 of the approximately 21,000 human genes. But until now, few studies have investigated whether homing in on a pre-determined panel of suspects can actually help people.

The researchers, medical oncologists and geneticists James Ford, MD and Allison Kurian, MD, used a customized 42-gene panel to investigate the presence of cancer-associated mutations in 198 women with a family or personal history of breast or other cancers. The women had been referred to Stanford’s Clinical Cancer Genetics Program between 2002 and 2012 to undergo screening for mutations in their BRCA1 or BRCA2 genes. They found that the panel was  a useful way to quickly screen and identify other cancer-associated mutations in women who did not have a BRCA1/2 mutation. From our release:

Of the 198 women, 57 carried BRCA1/2 mutations. Ford and Kurian found that 14 of the 141 women without a BRCA1/2 mutation had clinically actionable mutations in one of the 42 genes assessed by the panel. (An actionable mutation is a genetic variation correlated strongly enough to an increase in risk that clinicians would recommend a change in routine care — such as increased screening — for carriers.)

Eleven of the 14 women were reachable by telephone, and 10 accepted a follow-up appointment with a genetic counselor and an oncologist to discuss the new findings. The family members of one woman, who had died since giving her blood sample, also accepted counseling. Six participants were advised to schedule annual breast MRIs, and six were advised to have regular screens for gastrointestinal cancers; many patients received more than one new recommendation.

One woman, with a history of both breast and endometrial cancer, learned she had a mutation that causes Lynch syndrome, a condition that increases the risk of many types of cancers. As a result, she had her ovaries removed and underwent a colonoscopy, which identified an early precancerous polyp for removal.

The study shows that gene panels can be a useful tool that can change clinical recommendations for individual patients. It also indicates that patients are willing and eager to receive such information. As Ford explains in the release:

Gene panels offer a middle ground between sequencing just a single gene like BRCA1 that we are certain is involved in disease risk, and sequencing every gene in the genome. It’s a focused approach that should allow us to capture the most relevant information.

Previously: Whole genome sequencing: the known knowns and the unknown unknowns,  Assessing the challenges and opportunities when bringing whole-genome sequencing to the bedside and Blood will tell: In Stanford study tiny bits of circulating tumor DNA betray hidden cancers.

Addiction, Health Disparities, In the News, Public Health

Menthol cigarettes: How they’re being used by and marketed towards African Americans

Menthol pic - smallHere’s a scary statistic, included in a recently published Newsweek article: “Each year, smoking-related illnesses kill more black Americans than AIDS, car crashes, murders and drug and alcohol abuse combined, according to the Centers for Disease Control and Prevention (CDC).” And then there’s this: “More than four in five black smokers choose menthol cigarettes, a far higher proportion than for other groups… By mitigating the harshness of cigarettes and numbing the throat, menthol makes smoking more palatable, easier to start – and harder to quit.”

The article discusses advocates’ call for a ban on menthol cigarettes (all other flavored cigarettes were banned in 2009) before going on to describe the history of African Americans and menthol-cigarette use, and tobacco companies’ aggressive marketing tactics. (“The tobacco industry… positioned itself as an ally of the very community it was seducing,” writes Abigail Jones.) It also quotes Stanford’s Robert Jackler, MD, founder of Stanford Research into the Impact of Tobacco Advertising, who expresses his concerns with ads that appear in a prominent African-American publication:

…[Jackler] has analyzed Ebony magazines since the 1940s and discovered it ran 59 cigarette ads in 1990, 10 in 2011 and 19 last year.

Ebony published 21 articles about breast cancer and 11 about prostate cancer between 1999 and 2013 but did not publish a single full-length story on lung cancer in that 15-year period. “Tobacco advertising is a huge revenue stream,” says Jackler. “Ebony professes itself to be the so-called ‘heart and soul and voice of the African-American community,’ and it completely neglects smoking.”

Previously: E-Cigarettes: The explosion of vaping is about to be regulated, What’s being done about the way tobacco companies market and manufacture products, Menthol “sweetens the poison,” attracts more young smokers, Menthol cigarette marketing aimed at young African Americans and NPR’s Picture Show highlights Stanford collection of cigarette ads
Photo by Classic Film

Global Health, Pediatrics, Public Safety, Research, Stanford News, Women's Health

Empowerment training prevents rape of Kenyan girls

Empowerment training prevents rape of Kenyan girls

Adolescent girls in the slums of Nairobi, Kenya, are frequent targets of sexual harassment and assault: Nearly one in five of them is raped each year. When these crimes are perpetrated against Nairobi’s teen girls, they’re often expected to react with shame and silence.

But a small non-governmental organization, No Means No Worldwide, has a strategy to change that. The co-founders, Jake Sinclair, MD, and Lee Paiva, an American husband-and-wife team, developed a curriculum of empowerment training to teach girls that it’s OK to say “no” to unwanted sexual advances. The training also gives girls specific verbal and physical skills to defend themselves, as well as information about where to go for help after a rape or other sexual assault.

The results are impressive. Stanford researchers who work with Sinclair and Paiva report today in Pediatrics that the empowerment training cut annual rates of rape by more than a third. Among the group of 1,978 girls trained during the study, more than half used their new knowledge to fend off attempted rape, and 65 percent stopped instances of harassment, halting hundreds of incidents.

From our press release about the research:

“Clearly, girls should never be placed in these situations in the first place,” said Clea Sarnquist, DrPH, the study’s lead author and a senior research scholar in pediatrics at Stanford. Changing males’ attitudes and behavior about assault is an important area for the team’s current and future work, she said. “But with such a high prevalence of rape, these girls need something to protect them now. By giving them the tools to speak up and the knowledge that ‘I have domain over my own body,’ we’re giving them the opportunity to protect themselves.”

The video above, one of a series of testimonials that No Means No Worldwide has collected from Nairobi girls, shows the power of that sense of domain over one’s body. In the video, a schoolgirl named Catherine tells how she stopped a male student from harassing her. When the video begins, it’s impossible not to notice how young and vulnerable she seems. But then she recounts how, when this boy followed her and demanded sex, she remembered her self-defense classes.

“I stood and maintained eye contact,” she says in the video. “I warned him that day and told him he should never in his life dare follow me.”

As she says the words, her demeanor transforms: She draws herself up straight, looks directly in the camera, and raises her index finger in a gesture of commanding attention.

Maryanne Wangui, a young Kenyan woman who recorded many of the testimonials, said something to me that resonates with Catherine’s account and sticks in my mind: “If you give girls the right skills, they know what to do. It doesn’t matter the age of the girl or the size of the girl; they’re all powerful inside.”

Previously: Self-defense training reduces rapes in Kenya
Video courtesy of No Means No Worldwide

Grand Roundup

Grand Roundup: Top posts for the week of April 6

The five most-read stories this week on Scope were:

Stanford bioengineer develops a 50-cent paper microscopeManu Prakash, PhD, assistant professor of bioengineering, has developed an ultra-low-cost paper microscope to aid disease diagnosis in developing regions. The device is further described in a technical paper.

Music box inspires a chemistry set for kids and scientists in developing countries: Manu Prakash has also developed a chemistry set that can be built with materials costing about $5. The device won a contest from the Gordon and Betty Moore Foundation and the Society for Science & the Public to “Reimagine the chemistry set for the 21st century.”

Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers: A blood sample may one day be enough to diagnose many types of solid cancers, or to monitor the amount of solid cancer in a patient’s body, researchers in the labs of Stanford radiation oncologist Maximilian Diehn, MD, PhD, and hematologist and oncologist Ash Alizadeh, MD, PhD, have shown.

Art and anatomy: Decades-old collaboration brings augmented reality into the hands of Rodin: Stanford’s Cantor Arts Center launched a first-of-its-kind exhibit, “Inside Rodin’s Hands: Art, Technology, and Surgery,” which uses 21st Century technology to look inside the works of Rodin’s 19th Century sculptures.

Bad news for pill poppers? Little clear evidence for Vitamin D efficacy, says Stanford’s John Ioannidis: A large study of vitamin D led by John Ioannidis, MD, DSc, found that more well-designed studies and trials are necessary before firm conclusions can be drawn about its efficacy.

And still going strong – the most popular post from the past:

What are the consequences of sleep deprivation?: Brandon Peters, MD, an adjunct clinical faculty member at the Stanford Center for Sleep Sciences and Medicine, explains how lack of sleep can negatively affect a person’s well-being in this Huffington Post piece.

Research, Science, Stanford News

Getting a glimpse of the shape molecules actually take in the cell

Getting a glimpse of the shape molecules actually take in the cell

Working at a medical school, every day I talk to scientists who are discovering ever more intricately detailed information about our bodies and our cells. With these daily amazements about what we do know, it’s always good to be reminded of how much is still unknown.

Case in point, I recently talked with Xuesong Shi, PhD, a postdoctoral fellow in the lab of biochemist Dan Herschlag, PhD. He has been trying to understand the many configurations and structures molecules and complexes of molecules take on. This may seem a bit abstract, but what the molecules look like – how many different shapes they fold into and how they interact with each other – can provide information that explains both how molecules behave normally, and also why they fail to work properly in some diseases.

For a long time now most of the information we have about the shape and structure of molecules came from turning those molecules into crystals of rigidly packed, identical structures. That’s a technique called X-ray crystallography, which people at Stanford carry out using the powerful X-ray beams at SLAC.

Herschlag points out that X-ray crystallography has been extremely valuable for helping scientists understand the molecules that make up our cells. But the crystals don’t necessarily give the whole picture. For example, molecules are thought to take on many different shapes when forming complexes, not just the single shaped found in a crystal. “The idea is that molecules have many forms in solution,” Shi said. Some molecules also don’t form crystals well.

Shi has been tackling this problem using an X-ray interferometry technique developed in the lab of biochemist Pehr Harbury, PhD, who collaborated with Herschlag and Shi on the work. It involves attaching tiny gold particles to known locations on molecules – in this case a snippet of DNA. Then, by using X-rays to look at where the gold particles are in relation to each other, scientists can piece together the myriad shapes the molecules take on when freed from a crystal lattice.

Shi was first author on a paper published online March 31 in the Proceedings of the National Academy of Sciences describing this technique. He told me that although that paper investigated the structure of DNA, he hopes to use the technique to better understand a variety of molecules where knowing the myriad shapes the molecule takes on is essential for understanding its function.

Health and Fitness, Stanford News, Videos

How social connection can improve physical and mental health

How social connection can improve physical and mental health

Past research has shown that a lack of social connection may be a greater detriment to a person’s health than obesity, smoking and high blood pressure. In this TEDxHayward video, Emma Seppala, PhD, associate director of Stanford’s Center for Compassion and Altruism Research and Education, discusses these and other findings showing that maintaining strong social relationships can improve physical and mental health. Contrary to popular belief, she says, social connection has more to do with your subjective feeling of connection than how many friends you have.

Take a moment to watch the talk and learn how fostering compassion for others and yourself can increase social connection and, as a result, benefit your health.

Previously: How loneliness can impact the immune system, The scientific importance of social connections for your health and Elderly adults turn to social media to stay connected, stave off loneliness

Global Health, Infectious Disease, Technology

Health workers use crowdsourced maps to respond to Ebola outbreak in Guinea

Médecins Sans Frontières and other international aid organizations are furiously working to contain an outbreak of Ebola in Guinea and nearby African countries. Latest reports estimate that the virus has infected 157 people and killed 101 in Guinea alone.

A New Scientist story published today explains how health workers from Médecins Sans Frontières were initially at a disadvantage when they arrived in Guinea to combat the deadly virus because they only had topographic charts to use in pinpointing the source of the disease. Desperately in need of maps that would be useful in understanding population distribution, the organization turned to Humanitarian OpenStreetMap Team, which coordinated a crowdsourcing effort to produce the first digital map of Guéckédou, a city of around 250,000 people in southern Guinea. Hal Hodson writes:

As of 31 March, online maps of Guéckédou were virtually non-existent, says Sylvie de Laborderie of cartONG, a mapping NGO that is working with MSF to coordinate the effort with HOT. “The map showed two roads maybe – nothing, nothing.”

Within 12 hours of contacting the online group, Guéckédou’s digital maps had exploded into life. Nearly 200 volunteers from around the world added 100,000 buildings based on satellite imagery of the area, including other nearby population centres. “It was amazing, incredible. I have no words to describe it. In less than 20 hours they mapped three cities,” says de Laborderie.

Mathieu Soupart, who leads technical support for MSF operations, says his organisation started using the maps right away to pinpoint where infected people were coming from and work out how the virus, which had killed 95 people in Guinea when New Scientist went to press, is spreading. “Having very detailed maps with most of the buildings is very important, especially when working door to door, house by house,” he says. The maps also let MSF chase down rumours of infection in surrounding hamlets, allowing them to find their way through unfamiliar terrain.

Previously: Using crowdsourcing to diagnose malaria and On crowdsourced relief efforts in Haiti

Humor, Neuroscience, Research, Stanford News

Looking at how a child’s sense of humor takes its shape

Looking at how a child's sense of humor takes its shape

girl2Where does a child’s sense of humor come from? That depends on how you define humor and where you look to find it. A recent blog post from the Cognitive Neuroscience Society reports:

Humor can be a very complex and hard concept for some kids to grasp, said [Jessica Black, PhD,] of the Graduate School of Social Work Boston College, speaking yesterday about her poster on this new work at the CNS meeting in Boston. It requires people to both detect and resolve incongruities and to find amusement – involving many regions of the brain, including those that process cognitive computations and those that process emotions.

Black and others, including Allan Reiss, MD, the study’s director, and Pascal Vrticka, PhD, both of Stanford, studied how different brain regions were activated as children watched a video with funny, positive or neutral content. Twenty-two children ages 6 to 13 were asked to rate their ability to create and appreciate humor. Then, researchers examined their brain activity using fMRI scans.

The CNS blog post continues:

In general, the researchers found greater brain activity in children who rated themselves low on the sense of humor scale. The systems related to detecting incongruities and those involved in language and working memory had to ramp up to process the funny videos, as did the arousal network that is usually more active when processing negative emotional information. Interestingly, the brain activity related to social processing was lower in these children, suggesting perhaps more difficulty in being able to think about the mental state of others.

Their results suggest that children with a low sense of humor may require more cognitive effort to process humor, Black said. The data also imply that children with a low sense of humor may experience stress and increased levels of arousal during social interactions involving humor.

Previously: A closer look at the way our brains process humorHumor as a mate selection strategy for women? and Making kids laugh for science: Study shows how humor activates children’s brains
Photo by Maria del Carmen Gomez

Medical Education, Medicine and Society, Stanford News

Studying the humanities to address “the messiness of human life”

Studying the humanities to address "the messiness of human life"

Life’s problems and people are often complex, ambiguous and soft to the touch. This holds true even in the medical sciences and professions that require precision in data collection and analysis; critical thinking skills and a broad, flexible world view are therefore necessary components of a balanced education. The School of Medicine‘s dean, Lloyd Minor, MD, explains in a recent op-ed for the Stanford Daily why anyone invested or even interested in medicine should pay attention to the humanities.

From the piece:

Consider the child with autism or the adult with Alzheimer’s disease. A physician can make a diagnosis but cannot offer a cure or a satisfying answer to the question “why?” Even for conditions that we can prevent or treat, patient behavior can significantly impact the success or failure of an intervention. For the hypertensive patient, no amount of prescribed medication will impact the social factors that may be inhibiting lifestyle modification. The specificity of scientific interventions does not account for the messiness of human life.

We as physicians heal best when we listen to and communicate with our patients and seek to understand the challenges they face in their lives. The perspectives on illness, emotions and the human condition we gain from literature, religion and philosophy provide us with important contexts for fulfilling these roles and responsibilities.

Previously: Becoming Doctors: Stanford med students reflect and share experiences through podcastsThoughts on the arts and humanities in shaping a medical careerEncouraging alternative routes to medical school and Stanford dean discusses changing expectations for medical students

Autism, Genetics, Neuroscience, Research, Videos

Building a blueprint of the developing human brain

Building a blueprint of the developing human brain

In an effort to identify and better understand how genes turned on or off before birth influence early brain development, scientists at the Allen Institute for Brain Science have created a comprehensive three-dimensional map that illustrates the activity of some 20,000 genes in 300 brain regions during mid-prenatal development.

A post on the NIH Director’s blog discusses the significance of the project, known as the BrainSpan Atlas of the Developing Human Brain:

While this is just the first installment of what will be an atlas of gene activity covering the entire course of human brain development, this rich trove of data is already transforming the way we think about neurodevelopmental disorders.

To test the powers of the new atlas, researchers decided to use the database to explore the activity of 319 genes, previously linked to autism, during the mid-prenatal period. They discovered that many of these genes were switched on in the developing neocortex—a part of the brain that is responsible for complex behaviors and that is known to be disrupted in children with autism. Specifically, these genes were activated in newly formed excitatory neurons, which are nerve cells that send information from one part of the brain to another. The finding provides more evidence that the first seeds for autism are planted at the time when the cortex is in the midst of forming its six-layered architecture and circuitry.

In the above video, Ed Lein, PhD, an Allen Institute investigator, talks about the atlas and explains how it will allow researchers to examine genes that have been associated with a range of neurodevelopmental disorders and pinpoint when and where that gene is being used.

Previously: NIH announces focus of funding for BRAIN initiative, Brain’s gain: Stanford neuroscientist discusses two major new initiatives and Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute

Stanford Medicine Resources: