The Liposarcoma Genome Project started with seed money from a patient donor. Now it is poised to take sarcoma research to an exciting new place.

“A cure for one is a cure for all,” is the motto of the Liposarcoma Genome Project (LGP) at the Massachusetts General Hospital Cancer Center. The phrase reflects the fact that research on this uncommon form of cancer could shed light on a range of other cancers as well, including many aggressive sub-types of sarcoma that have resisted the best efforts of doctors and researchers around the globe.

The research has the potential to impact not only the 375,000 people worldwide with liposarcoma, but patients with other types of cancers as well.

To this end, a survivor of liposarcoma — a rare and often deadly soft tissue cancer — has offered to match up to $500,000 in donations from the public for a total of $1 million to drive liposarcoma research forward at the Mass General Cancer Center.

Liposarcomas may arise anywhere in the body and occur in both a low-grade, well-differentiated form and a more aggressive, high-grade, dedifferentiated form.

While the five-year survival rate of dedifferentiated liposarcoma is less than 50 percent, the donor, who wishes to remain anonymous, has survived this aggressive form of the disease for almost 20 years, with sporadic remissions and continual treatments at the Mass General Cancer Center. He credits his doctors and researchers, and their distinctive team approach to treatment, for his beating the odds for so long.

Cutting-Edge Research

Researchers at the Liposarcoma Genome Project are working to understand the differences between the well-differentiated and dedifferentiated variants of the disease by conducting comprehensive profiling of the genetic and epigenetic (non-DNA-driven) alterations of these tumors.

Bradley Bernstein, MD, PhD
Bradley Bernstein, MD, PhD

To do so, they use fresh tissue samples from Mass General liposarcoma patients, says LGP lead investigator Sarah Johnstone, MD, PhD, a clinical and research fellow at Mass General.

“It’s hard for scientists to get funding for a study like this without preliminary data, and the seed money has allowed us to generate data that is now bringing new understanding to this disease,” Dr. Johnstone says.

“The Liposarcoma Genome Project is bringing cutting edge technologies to bear on a poorly understood disease. This is only made possible with the support of generous donors who have the vision to see the potential of today’s research to advance cancer treatment in the future,” says Bradley Bernstein, MD, PhD, a professor of Pathology at Mass General and Harvard Medical School, an Institute Member of the Broad Institute of MIT and Harvard, and LGP project director.

Aggressive Liposarcoma Treatment

Carol Scarpaci, shown with husband Frank Scarpaci, is cancer free following treatment at Mass General Cancer Center.
Carol Scarpaci, shown with husband Frank Scarpaci, is cancer-free following treatment at Mass General Cancer Center.

Mass General Cancer Center is a leading treatment center for liposarcomas and other types of sarcomas, offering cutting edge care and innovative treatments.

Carol Scarpaci is a liposarcoma patient of John Mullen, MD, a surgical oncologist and clinical and translational cancer researcher at the Mass General Cancer Center who specializes in the surgical treatment of sarcomas. Shortly after being diagnosed with a liposarcoma at age 66, Ms. Scarpaci had a course of intensive, high-dose radiation therapy followed by a complex, eight-hour surgery to remove not only the tumor but also those organs and tissues abutting it. This included part of her bowel, a kidney, and some blood vessels to her leg.

Mass General oncologists take this aggressive treatment approach “in an effort to prevent the cancer from recurring and from potentially morphing into the more deadly dedifferentiated form,” Dr. Mullen says.

“It’s a very difficult disease to treat. The tumors are often large and invasive — and they tend to come back,” Dr. Mullen says. “So when we can, we throw the kitchen sink at it, rather than chip away at the cancer only to have it recur and then have to put patients through multiple surgeries to treat the recurrences.”

Two years later, Ms. Scarpaci is cancer-free. Although a recurrence of the tumor is certainly still possible, she and Dr. Mullen are highly optimistic. “My doctors tell me my Rockette days are probably behind me — no high-kicking — but I walk every day, am back at work and I feel fine,” she says.

A Clue in Epigenetics

If we can understand the epigenetic switch that turns the tumor into the more deadly variety, it will be a potentially lifesaving switch that we could turn off for these patients.

The collaborative research team of physicians and scientists at the LGP aims to understand how liposarcoma tumors transform from the low-grade, well-differentiated form into the more lethal, high-grade, dedifferentiated form.

Using tissue samples taken by Dr. Mullen during surgery, they profile genetic sequences along with epigenome information, which essentially tells the genome what to do, including which genes to turn on or off. They hope to identify key mechanisms involved in tumor transformation.

Recently, the team made a surprising discovery—there is no main genetic mutation that distinguishes the two different types of liposarcoma. This is of great interest because it suggests that the differences between the subtypes are driven by epigenetic factors such as the proteins that control gene activity in the tumor cells. The team is studying these proteins with a technique called chromatin immunoprecipitation and sequencing, and now they have a wealth of data which they are currently analyzing.

Dr. Johnstone is excited by the epigenetic factors of the tumor transition. “Epigenetic factors are more malleable, and plastic, than genomic factors, so this is an exciting therapeutic avenue,” she says. “If we can understand the epigenetic switch that turns the tumor into the more deadly variety, it will be a potentially lifesaving switch that we could turn off for these patients.”

Stepping Stone to Future Therapies

Their findings, Dr. Johnstone says, have the potential to impact not only the 375,000 people worldwide with liposarcoma, but patients with other types of cancers as well. “Understanding the genetic drivers of liposarcoma can shed light on several types of sarcomas and even other cancers, such as carcinomas, as well,” she says. The potential of $1 million in funding will further their work and support international collaborations.

Future therapies could forge a healthy future for patients like Ms. Scarpaci, who has lately had more time to think about other things. “I can just focus on watching my six grandchildren grow,” she says.

For more information about the Liposarcoma Genome Project or to make a donation that will be matched dollar-for-dollar by an anonymous donor, please contact us.