Diagnosed with rare genetic mutation, student attends ASU Law to help reform health insurance


August 1, 2019

When she was 5, doctors gave Claudia Reeves' parents a dire warning: Without reconstructive surgery, their daughter's face was at risk of collapsing.

Reeves was diagnosed with the rare genetic mutation — oligodontia — that has shaped her life ever since. Oligodontia, which is estimated to affect less than 0.1% of the world’s population, is the absence of more than six primary teeth. photo of Claudia Reeves Claudia Reeves (at left) as a child and today. Reeves was diagnosed with a rare genetic mutation that has shaped her life in profound ways. Download Full Image

“I spent the next 13 years in every mouth device ever invented,” the now 22-year-old said. “Braces, rubber bands, bondings, palette expanders, flipper teeth, winged teeth, implants, bridges.”

On the advice of her doctors, she finally had facial reconstructive surgery four years ago. But the bad news didn’t end there. The surgery would not be covered, as insurance companies deemed it “cosmetic.” The total out-of-pocket expense? Around $150,000.

“Doctors were unsure how I could eat and maintain proper nutrition since my back teeth did not touch and I had little teeth function,” she said. “My teeth never grew larger than the size of an 8-year old’s. My health suffered as I was not able to eat a majority of foods.”

Nevertheless, insurance companies still did not deem her surgery a medical necessity.

photo of dental items

As doctors tried to help, Reeves gathered a vast collection of dental devices over the years.

There was nothing elective about the surgery to Reeves, and she is thankful she had the means to pay for it. She is now in better health and finally getting to experience simple pleasures that others take for granted.

“Four years ago, I was able to bite into an apple for the first time,” she said.

The dilemma has inspired her to help others avoid the same difficulties.

Now entering her second year at the Sandra Day O’Connor College of Law at Arizona State University, Reeves is seeking a career in health law — to honor the doctors who treated her and to help clear legal obstacles for others with serious health challenges.

“I want to pursue a career in health law,” she said. “My goal is to eventually be in-house counsel for a hospital and to get insurance companies to provide more funding for genetic mutations and disabilities.”

Originally from Overland Park, Kansas, she remembers telling her mother at age 13 that she was going to be a lawyer. She went on to attend the University of Arkansas, structuring her college experience around her goal.

She minored in insurance and worked at Allstate for more than three years so that she could have both textbook knowledge and practical application of the insurance industry. And anxious to start what she had been dreaming of since she was 13, she finished her undergrad studies in just three years and then set her sights on ASU Law.

“I was led to ASU Law because it was ranked No. 25 in the country and I really wanted to attend a law school that had influence in the legal world,” she said. “Dean Sylvester made a touching speech at Admitted Students Day about how ASU Law would be unlike any other law school in the nation in that the law school would tailor itself to the diversity of the students and would capture every niche. Those words made me feel at home and captured the values of a law school I wanted to attend.”

This summer, she continued working toward her career goal with an externship at the Phoenix office of the Equal Employment Opportunity Commission (EEOC).

“I was interested in working for the EEOC this summer because I was fascinated with how the EEOC promulgates different guidelines for discrimination that is prohibited by Title VII,” she said. “I’m particularly interested in those cases regarding discrimination because of disability.”

It’s an experience that has validated her career decision — and one that she would recommend to other students.

“The experience so far has been wonderful,” she said. “All of the attorneys at the Phoenix office have taken great strides to make sure that I get exposure to various forms of legal research and writing. Because I have no attorneys in the family, and have done no other legal externships, I was terrified that I may not make a good attorney because I have had zero experience outside of class. From the beginning, the attorneys, paralegals and investigators have made me feel so valued, appreciated and capable. I can now say positively that I am in the right career field.”

Reeves said the first year at ASU Law was a bumpy ride, but a rewarding one, and credits the two mandatory legal writing classes for first-year students with giving her the tools to effectively research and write a memo. And she has advice to offer for future first-year law students who at times may feel overwhelmed by the challenge of being surrounded by so many talented peers.

“Everyone in that room is used to being the very best at everything they do,” she said. “It gets easy to question your self-worth when you get your first 'B' or even 'C.' I know I questioned my worth when I got my midterm grades back. Despite what your GPA reads at any point in the first year, you must know you have been given that seat for a reason. You are going to be surrounded by doctors, judges, actors, child prodigies. Remind yourself that you are sitting amongst a very intelligent and fascinating group of people because you are someone with an incredible story of your own. Own that story — and if you ever need someone to talk to, I am here.”

Nicole Almond Anderson

Director of Communications, Sandra Day O'Connor College of Law

480-727-6990

Cancer without end? Discovery yields fresh insights


August 1, 2019

If there is any consolation to be found in cancer, it may be that the devastating disease dies with the individual carrying it. Or so it had long been assumed. Recent research, however, has uncovered some forms of cancer that are transmissible, jumping from one host to another. Indeed, one such contagious cancer, known as canine transmissible venereal tumor (CTVT), has managed to persist in dogs for thousands of years.

In a new commentary appearing in the Aug. 2 issue of the journal Science, Arizona State University's Carlo Maley and University of Southern California's Darryl Shibata describe the dynamics of this sexually transmitted disease, which arose in a single ancient animal, living as much as eight-and-a-half millennia ago. CTVT first emerged in a dog that lived 4,000-8,500 years ago. All CTVT tumors carry the DNA belonging to this “founder dog." By counting and analyzing the mutations acquired by CTVT tumors around the world, researchers can piece together how and when CTVT emerged and spread. Artist’s impression of the “founder dog” that first gave rise to CTVT. This dog’s phenotypic traits were interpreted from the genetic variation found in the DNA of the cancer that it spawned. Image credit: Emma Werner Download Full Image

Intriguingly, the exploration of long-term, multigenerational cancer evolution in CTVT may shed new light on how human cancers evolve during the typical course of the disease and may inspire new approaches to treating cancer, which remains the second leading cause of death worldwide.

“Cancers evolve, and our strategies for managing cancer need to take that into account,” Maley said. In the future, we hope to maintain long-term control over these evolving tumors. CTVT is fascinating because it shows us how cancers might evolve over the long term.”

Maley is a researcher in the Biodesign Center for Biocomputing, Security and Society, the Center for Immunotherapy, Vaccines and Virotherapy and the Center for Mechanisms of Evolution at Arizona State University, as well as ASU’s School of Life Sciences. He is the director of the newly established Arizona Cancer and Evolution Center (ACE). Shibata is a professor in the Department of Pathology at USC and the co-director of the ACE Center.

Ominous signs emerge

Examples of contagious cancers in humans exist, but they remain exceedingly rare and have never spread beyond a second host. Other animals are less fortunate and may fall prey to a range of transmissible cancers, which vary in the severity of their impact.

In 1996, a mysterious illness began sweeping through animal populations in the central highlands of Tasmania. The island’s Tasmanian devils were dying from a gruesome facial tumor. At first, a virus was the suspected culprit in the rapidly spreading epidemic. But when the DNA fingerprints of afflicted devils were examined, researchers made a remarkable discovery. The tumor cells were genetically distinct from the devil’s own healthy cells, yet they matched tumor cells taken from other Tasmanian devils with the facial tumor disease. It was as though the tumor cells had been cloned and transplanted into each stricken animal. The disease was positively identified as an aggressively lethal, transmissible cancer.

The current commentary concerns CTVT, which causes grotesque, oozing tumors that afflict the genital area in dogs. When researchers sequenced cells from these tumors, the results mirrored those observed in the Tasmanian devils. All of the cancer cells shared a suite of genetic variants that did not appear in the dogs’ healthy cells. This led to a startling conclusion: CTVT is not simply a disease that occasionally develops in dogs. It arose only once, in a single dog and has been transmitted through the ages from one animal to the next ever since.

When two dogs with CTVT were examined, one in Brazil and another in Australia, each belonging to a different breed, their tumor cells shared nearly 2 million mutations that were not found in normal canine DNA. While the CTVT genome diverged considerably from the original dog genome, it remained remarkably stable over time.

A contagious form of cancer known as canine transmissible venereal tumor (CTVT) has been affecting dogs for thousands of years. The evolution of this disease could hold vital insights for the study and treatment of human cancers.

Dog years

Unlike the pitiless cancer devastating the Tasmanian devils, CTVT is rarely lethal. Instead, it typically persists for a matter of months before being cleared by the dog’s immune system. (See drawing based on genetic sequencing of what the first dog carrying CTVT may have looked like.)

Recent investigations of CTVT, carried out by Adrien Baez-Ortega and colleagues, advance the unusual story of this disease. Their findings appear in the current issue of Science and are the focus of Maley and Shibata’s commentary. 

Baez-Ortega, a researcher at the University of Cambridge, sequenced tumors from 546 dogs around the world. The results showed the great antiquity of CTVT, which has been transmitted by dogs for 4,000 to 8,500 years. For evolutionary biologists like Maley and Shibata, the findings are revelatory, in part because CTVT appears to have stopped evolving long before it spread around the world.

New directions

The study of cells derived from transmissible cancers like CTVT provides valuable clues for biologists interested in the development of human cancers. Examining somatic cell evolution around the world and over significant spans of time helps researchers understand the subtle dynamics of the evolutionary processes involved in cancer. (In contrast, observing the life and death of cells over time in an individual patient is very difficult.)

Perhaps the most critical observation resulting from the genome sequencing of CTVT is that cancer is not an inevitably progressive disease. Rather, tumors may reach an optimal state that can stabilize over time, exhibiting little or no additional gains in biological fitness — the ability to survive and reproduce.

Typically, tumors persevere and wreak havoc by generating numerous mutations. While most of these have no effect on cancer cell survival, or are even harmful, a few convey an adaptive advantage to cells, increasing their survivability. These are known as driver mutations and as the name implies, they are responsible for a successful cancer’s relentless expansion. Driver mutations generate the cells that are able to resist cancer treatment.

It appears that CTVT has been evolving neutrally after its inception, accumulating mutations that do not affect fitness. The successful development of CTVT in dogs therefore seems to require only a few minor adjustments to the genome. The lack of ongoing natural selection in CTVT also suggests that the disease has not had a significant impact on dog survival and reproduction.

The stability of CTVT over time offers hope that certain slow-growing human cancers resistant to conventional therapy, for example prostate cancer, could be tamed and controlled. This might be achieved through so-called adaptive therapies, which seek to limit tumor growth as opposed to aggressive treatments aimed at total eradication, which invariably select for resistant and often lethal cell variants. A pilot clinical trial to test this approach in metastatic breast cancer will soon start at Mayo Clinic’s Arizona campus, in collaboration with ASU.                                             

It seems likely that ongoing explorations of cell evolution in CTVT will provide further insights into complex cell trajectories and genetic transformations in a range of human cancers and inspire innovative methods of addressing the disease.

“Most cancers can only evolve for a few decades before they die with their host,” Maley said. “CTVT is an incredible natural experiment, which showed us that it doesn’t take much for a cancer to reach an optimal state. It is amazing that it did not discover additional adaptations over thousands of years, even as it infected all different breeds of dogs in all different environments around the world.”

Richard Harth

Science writer, Biodesign Institute at ASU

480-727-0378