Published by
Stanford Medicine

Applied Biotechnology, Cancer, Genetics, otolaryngology, Research, Stanford News

Stanford researchers identify genes that cause disfiguring jaw tumor

Stanford researchers identify genes that cause disfiguring jaw tumor

jawPatients with the rare jaw tumor ameloblastoma have few treatment choices. Radiation and drugs have failed to stop this slow-growing cancer, leaving jaw removal as the only option. The surgery also takes out facial nerves and blood vessels, and so patients need reconstructive surgery and rehabilitation just to smile and chew again.

In a new study, published in Nature Genetics, Stanford researchers discovered two gene mutations that cause this tumor. Their findings point to FDA-approved drugs that are effective against these mutations in other types of cancer.

To find the mutations, the researchers sequenced mRNA – messages copied from genes that tell the cell how to make proteins – from slices of preserved tumor. In 80% of the samples, they found a mutation in either the SMO or the BRAF gene. Interestingly, the SMO mutations occurred predominantly in the upper jaw, while BRAF mutations were found mainly in the lower jaw.

From our press release:

“These genes are essential for delivering signals of growth and development, particularly in developing organs,” said Robert West, MD, PhD, associate professor of pathology at Stanford and a senior author on the study. “But it’s increasingly apparent that they are often mutated in cancers.”

Perhaps most promising, researchers found that there are already FDA-approved drugs for cancers with mutations in the same developmental pathway. A drug called vemurafenib is toxic to ameloblastoma cell cultures that harbor a BRAF mutation, they found. This drug is effective against melanomas that carry the same mutant gene. Researchers also found that a compound called arsenic trioxide, an approved anti-leukemia drug, is affective at blocking the mutant SMO protein.

West and his colleagues, A. Cain McClary, MD, a co-author and chief pathology resident at Stanford Hospital, and A. Dimitrios Colevas, MD, an associate professor of oncology at Stanford, have already submitted an application to the biotech company Genentech, which manufactures the most popular brand of vemurafenib. Their pilot study would test whether the drug could shrink tumors in people with ameloblastomas.

Also from the release:

Throughout this project, McClary has engaged with an ameloblastoma Facebook group to hear members’ stories and to learn about what a patient goes through during the initial surgery and subsequent facial reconstruction. He plans to conduct a webinar with the group, and can’t wait to share his findings with them.

“It’s a great motivator,” he said about his involvement with the group. “Our face is a special place. I couldn’t imagine not smiling.”

Patricia Waldron is a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Gene panel screens for dozens of cancer-associated mutations, say Stanford researchers
Photo by Gray’s Anatomy Plates/Wikimedia Commons

Comment


Please read our comments policy before posting

Stanford Medicine Resources: