Public Release:  OHSU Cancer Instutute researchers find abnormalities in gene for melanoma

Discovery could lead to effective treatments for host of previously untreatable melanomas

Oregon Health & Science University

PORTLAND, Ore. - New research from the Oregon Health & Science University Cancer Institute about mutations in melanoma may bring a wellspring of hope to many patients.

Researchers have discovered that there are several different kinds of DNA abnormalities that can occur in a gene called the KIT gene. These abnormalities are associated with different kinds of acral and mucosal melanomas, which are less common, but highly malignant forms of skin cancer. Acral melanomas are found on the palms of hands, the soles of feet and under nails. Mucosal melanomas are found in the mucous membranes of some organs of the body.

If scientists can figure out the mutation, effective treatments can follow, explained Michael Heinrich, M.D., co-principal investigator, OHSU Cancer Institute member and head of the Hematology and Medical Oncology Section at the Portland Veterans Affairs Medical Center. The co-investigator is Christopher Corless, M.D., Ph.D., OHSU Cancer Institute member.

The research will be presented Sunday, June 1, at 5 p.m. during the annual American Society of Clinical Oncology in Chicago.

This study builds on recent research about the first instance in which a woman's metastatic melanoma was driven into remission by the targeted therapy drug, Gleevec, which was developed at the OHSU Cancer Institute. Previously there had been few effective treatments for melanoma patients with metastatic disease. But not all melanomas respond so successfully to Gleevec.

In the current study, Heinrich and colleagues studied 129 samples gathered from people with different types of melanoma and found that there is a high rate of mutations in these cancers.

"This means that if we can find the melanoma early, it can be screened to see what type of mutations are present, and eventually you can get the right medication or treatment," Heinrich said.

Heinrich explained that it is similar to testing of breast cancer tumors to decide if patients should receive specific treatments such as hormonal inhibitors and/or the drug Herceptin. He predicts that drugs to treat the mutations found in melanomas could be developed in as little as 18 months.

'In the very near future, we can do DNA testing of melanomas to better know exactly what is driving the growth of the cancer and select the best treatment. When we know what is wrong, we can do something to fix it," Heinrich said.

The same KIT mutations as those found in gastrointestinal stromal tumors (GIST) are present in mucosal and acral melanomas. Gleevec's effectiveness against tumors with KIT mutations was first demonstrated by Heinrich. Recent studies have found KIT mutations in 11 percent of acral melanomas 21 percent of mucosal melanomas and 17 percent of melanomas arising in sun-damaged skin.

Melanoma is found predominantly in skin but also in the bowel and the eye. It is the most serious type of cancer of the skin. Each year in the United States, more than 53,600 people learn they have melanoma and the percentage of people who develop melanoma has more than doubled in the past 30 years, according to the National Cancer Institute.

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Other researchers involved in this research include: C. Beadling, Ph.D., Portland Veterans Affairs Medical Center, Portland, Ore.; B.P. Rubin, M.D., Ph.D., Cleveland Clinic, Cleveland, Ohio; S. Muller, M.D., D.M.D., Emory University School of Medicine, Atlanta Ga.; and F.S., Hodi, M.D., Dana-Farber Cancer Institute, Boston, Mass.

This research is funded by a United States Department of Veterans Affairs Merit Review Grant.

Particulars: Heinrich is also professor of medicine (hematology/medical oncology), and interim head of the Division of Hematology/Medical Oncology, OHSU School of Medicine. Corless is a professor of pathology, anatomic pathology, OHSU School of Medicine.

The OHSU Cancer Institute is the only National Cancer Institute-designated center between Sacramento and Seattle. It comprises some 200 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 300 clinical trials conducted at the OHSU Cancer Institute.

Oregon Health & Science University is the state's only health and research university, and Oregon's only academic health center. OHSU is Portland's largest employer and the fourth largest in Oregon (excluding government), with 12,400 employees. OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves patients from every corner of the state, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to every county in the state.

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