Nav: Home

Moffitt Researchers complete largest genomic analysis of Merkel cell carcinoma patients

August 20, 2019

TAMPA, Fla. - Merkel cell carcinoma (MCC) is a rare, aggressive skin tumor that is diagnosed in approximately 2,000 people each year in the United States. Since MCC affects so few people, it is difficult to study the genetic factors that lead to its development and how those factors correlate with response to therapy. However, Moffitt Cancer Center researchers have developed the largest descriptive genomic analysis of MCC patients to date, in collaboration with Foundation Medicine and the Dana Farber Cancer Institute. Their analysis, published in Clinical Cancer Research, will provide important information to improve the care and treatment of MCC patients for many years to come.

Researchers are beginning to learn more about how MCC develops and its associated risk factors. Many patients with MCC have mutations within their DNA that are caused by UV radiation exposure, demonstrating that exposure to natural or artificial sunlight increases a person's risk. Additionally, DNA and proteins from the virus Merkel cell polyomavirus (MCPyV) are present in many patients with MCC, and it is now accepted that MCPyV plays an important role in MCC development in some cases.

In the past, patients with MCC had few effective treatment options, resulting in a poor prognosis with a 5-year survival rate of only 20%. However, Todd Knepper, PharmD, assistant member of the Department of Individualized Cancer Management at Moffitt, says that MCC patients now have hope for improved outcomes. "Just a few years ago there were no FDA-approved treatments for patients with MCC, but recently the treatment paradigm for advanced MCC has shifted dramatically with immune checkpoint inhibitors demonstrating remarkable efficacy in this disease," said Knepper. "Indeed, since 2017 several immune checkpoint inhibitors have been approved for the treatment of patients with MCC, and clinical data have demonstrated their ability to improve patient response rates and survival."

With these improvements in the understanding of MCC biology and therapeutic advances in immunotherapy, the Moffitt researchers wanted to generate a more comprehensive analysis of patients with MCC to understand its genetic landscape and how these genetic differences affect treatment responses. They performed a comprehensive genomic analysis of 317 patients with MCC, and also analyzed the outcomes of 57 MCC patients treated at Moffitt. Importantly, they also compared these genetic profiles to other skin cancers showing that MCPyV-positive MCC resembles other viral cancers whereas MCPyV-negative MCC resembles other neuroendocrine cancers.

The researchers reported that there were two distinct populations among the 317 MCC patients - patients with a high tumor mutational burden (TMB) and those with a low TMB. Of the patients with a high TMB, 94% had a UV-signature mutation in their tumor DNA and none of these patients had evidence of MCPyV. On the other hand, patients with a low TMB did not have a UV-signature mutation, but rather 63% of these patients had evidence of MCPyV virus within their tumors. Among both TMB-high and TMB-low tumor populations, mutations in the genes TP53 and RB1 were the most prevalent.

In their analysis of treatment outcomes, the researchers discovered that immunotherapies were highly effective for patients with both a high TMB and a low TMB; 50% of patients with TMB-high/UV-driven tumors had a response to therapy while 41% of patients with TMB-low/MCPyV-positive had a response to therapy. Importantly, the researchers found that the earlier the patients were treated with immunotherapy, the better they responded to therapy. The percent of MCC patients who responded to immunotherapy when given as their first treatment was 75%, but the response rate decreased to 39% for those treated with immunotherapy as their second therapy and 18% for those treated as their third or later therapy. The researchers also reported that patients who expressed the biomarker PD-1 had a better response to immunotherapy than patients who did not express PD-1.

Prior to the Moffitt study, the largest analysis of MCC patients included fewer than 50 patients. According to Andrew Brohl, MD, assistant member of Moffitt's Cutaneous Oncology Department, "This study represents the largest description of the genomic landscape of Merkel cell carcinoma. The magnitude of this study provides a more definitive landscape of the disease, demonstrating the distinctive mutational spectra of MCPyV-positive/TMB-low and UV-driven MCC subgroups. While there are two distinct molecular subsets of this disease, interestingly, they exhibit similar response rates to checkpoint inhibitor therapy."
The study was supported in part by the National Cancer Institute Cancer Center Support Grant (P30-CA076292), the Campbell Family Foundation, the DFCI Helen Pappas Merkel Cell Research Fund and the Claudia Adams Barr Program in Cancer Research.

About Moffitt Cancer Center

Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 51 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's scientific excellence, multidisciplinary research, and robust training and education. Moffitt is a Top 10 cancer hospital and has been nationally ranked by U.S. News & World Report since 1999. Moffitt devotes more than 2 million square feet to research and patient care. Moffitt's expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 6,000 team members, Moffitt has an economic impact in the state of $2.5 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit, and follow the momentum on Facebook, Twitter and YouTube.

H. Lee Moffitt Cancer Center & Research Institute

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at