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Scientist hopes to further sarcoma research with help of tumor from a gibbon

Photo Credit: TIMES PHOTO: JAIME VALDEZ - Lucia Carbone, Assistant Professor in the Behavioral Neuroscience Department at OHSU, sits in the bay where her crew works.“I don’t know what it is, but I think they sent you a dead frog,” the delivery man told Kimberly Nevonen, a research assistant at the Oregon National Primate Research Center on Northwest 185th Avenue.

“What?” Nevonen responded, confused. But what she found inside the package was even weirder: a tumor. No description. No explanation. No note. And yet, there it was.

The tumor came from the Gibbon Conservation Center in Santa Clarita, Calif., an organization that ONPRC Assistant Scientist in Neuroscience Lucia Carbone has worked with for years. They send her samples of leftovers from things such as routine blood drawings or check-ups, which she and her team can then analyze and catalog, adding to their knowledge of the endangered primate.

This tumor, though. This tumor was unlike anything they’d ever received.

“Basically, they excised the whole thing; it was a nine-centimeter tumor. So they sent us this huge tumor. They didn’t tell us where it was from. They were just like, ‘Can you find a cure for this?’ We were like, ‘OK, what is it?’ I got really interested immediately,” Carbone said. “One of the things I claim that I think is true, is the gibbon is an awesome model for studying human cancer genomics, just because of the similarities, the chromosomal rearrangements.”Photo Credit: SUBMITTED PHOTO: ALISSA WHELAN - Ricky and one of her babies, Dennis, live at the Gibbon Conservation Center in Santa Clarita, Calif. Ricky has a specific kind of sarcoma on her foot, that researchers are hoping may shed new light onto the cancer.

Chromosomal rearrangements are the focus of much of Carbone’s research, and she’s spent years trying to get to the root of what makes them occur. The rearrangements come in four different types, she said, and are the reason for why chromosomes break. This breakage can lead to cancer and comes in the form of: deletion (two pieces are lost), duplication (two pieces are duplicated), translocations (two chromosomes are exchanging pieces) and inversion (a segment breaks and turns 180 degrees). Gibbons have an abundance of these chromosomal rearrangements.

“My interest is in the basic question: Why do chromosomes break? And why do chromosomes break more often? What are the traits in the genome that cause chromosomes to break more often than normally?” Carbone said. “Then, I try to figure out the consequences and what this leads to. I’m just very interested in why genomes are not stable, and they reshuffle in this way. So the gibbon was one way to study that, because of the particular feature that they have.”

After two years of research, Carbone had an article published in the September issue of Nature magazine that dove into some of these questions. She was chosen to lead the research team for the project, an anomaly as usually only those within the Gibbon Conservatory are picked to lead. Their findings, which received international attention, focused on why gibbons have so many chromosomal rearrangements, if they could discover the order of separation between the four gibbon species, and if they could pinpoint some of the unique, gibbon-specific traits.

After the article’s long-anticipated release, Carbone could turn her attention back to the tumor, which she still knew so little about. They learned the tumor came from the foot of a Gibbon named Ricky, was removed, but grew back immediately. What they later found out, after soliciting help from Oregon Health and Science University pathologists and oncologists, was that it was a malignant peripheral nerve sheath tumor, a type of sarcoma. Then they identified a human patient who has a sarcoma tumor with very similar characteristics.

“Nonhuman primates rarely get cancer in captivity because they have a low-fat diet, they are not exposed to pollution or toxic agents. They’re very protected,” Carbone said.

“And even in the wild, they might die before we would know,” Nevonen added.

“So it’s really hard to study. I looked in the literature, and there is very little about it,” Carbone said. “And from a gibbon, for sure not. When we got that, I was like, ‘OK, we need to do something about it because I want to sequence it. I want to see what the DNA looks like. But we didn’t have the funds to do that.”

That’s when one of the oncologists suggested contacting the Northwest Sarcoma Foundation, a nonprofit that in part looks for opportunities to invest in sarcoma research.

“We don’t have a lot of money to give for research, so we need to be very careful and strive for ones that have ripple effects,” said Tammy Wilhoite, executive director of the foundation. “Ultimately, we would like to see some sort of education come out of the RNA and DNA sequencing that will allow for anything that takes place with the gibbon to be applied to a human situation. Learning more about how sarcoma works can lead to better treatment outcomes.”

The money awarded totaled $15,000, which both Wilhoite and Carbone admitted is not a lot in the world of research, but enough to do the necessary sequencing. Much of that money came out of the Northwest Sarcoma Foundation’s Dragonslayer Walk, said Wilhoite, which takes place annually in Tigard’s Cook Park. The next step now is to sequence and identify the mutations in both the human and gibbon cancers.

“My idea for this project is if we can compare gibbon and human sarcomas, what is similar is supposed to be important for the sarcoma to be there, right? It’s kind of an evolutionary pathway. Because you find it in two different species, but the outcome, the phenotype is the same. It’s the cancer,” Carbone said. “Can we find a common pathway that takes the cells there?

“You could do this comparing a bunch of patients and similarities — it’s way more powerful if instead of comparing patients that are all human, you’re comparing different species and finding similar things. So that’s my hope.”Photo Credit: TIMES PHOTO: JAIME VALDEZ - Lucia Carbone, Assistant Professor in the Behavioral Neuroscience Department at OHSU, holds up a Nature magazine that featured her research project of chromosomal rearrangements.

Funding research

According to Tammy Wilhoite, executive director of the Northwest Sarcoma Foundation, sarcoma research receives few funds and little attention. The treatments are out of date and have low success rates, but patients have few options except to try.

“We are privileged to have an opportunity to affect the future of sarcoma research because our donors trust us with their hard-earned money. We take this responsibility very seriously, and we do our best to find projects of significance that will benefit sarcoma research,” Wilhoite said. “The Gibbon Sarcoma Project is an exciting opportunity for sarcoma research, and we are honored to be involved in this way.”

Because of this, the foundation is dedicated to raising money that it can invest into sarcoma research projects it believes in and thinks have the potential for lasting impacts. The $15,000 donated to scientist Lucia Carbone and her team is hoped to advance sarcoma research, and if funds are met, will eventually be doubled through the Knight Cancer Challenge.

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