A study published in Cancer Cell describes the identification and functional characterization of proteins that confer metastatic and invasive properties to early stage primary melanomas, the most deadly form of skin cancer in humans. The studies were conducted in the laboratories Lynda Chin, M.D., and Ron DePinho, M.D., from the Belfer Institute for Applied Sciences and Dana Farber Cancer Institute, and David Rimm, M.D., Ph.D. of Yale University. The researchers are the Scientific Founders of Metamark Genetics, Inc., a privately-held oncology-focused molecular diagnostics company.

“The findings from this study represent an important milestone in our efforts to predict whether or not an early melanoma lesion will eventually progress to metastatic and deadly disease,” said Dr. Chin. “Moreover, since these proteins are functionally involved in the tumor progression, they are also potential drug target candidates.”

Arising from moles
Melanoma is a form a cancer that originates in pigment-forming cells, or melanocytes, and is most commonly found in the skin where it typically arises from moles. In the United States alone, there were 68,130 new cases of melanoma last year, and approximately 8,700 deaths from the disease.

Six crucial genes
Cancer Cell study investigators utilized a novel approach that involved integrating results from refined, genetically engineered mouse models with human cancer data and subsequent functional studies. The researchers were able to identify and validate six genes that are crucial for invasion and metastatic behavior of cutaneous melanomas.

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Aggressive behavior of melanoma
“We believe that these findings significantly contribute to our molecular understanding of malignant melanoma with the potential to improve methods of defining prognosis and selection of optimal treatment strategies for patients with this disease,” said Dr. Chin. “Our functional studies show that these proteins are driving the aggressive behavior of melanoma. Further, when they are expressed across other tumor types they may play a similar role. This is supported by the fact that when we analyzed human breast cancer samples, some of these proteins were also able to predict the prognosis for patients with these tumors.”

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Early stage melanoma
Metamark has exclusively licensed a portfolio of technologies, including those described in this manuscript, from the Dana Farber Cancer Institute. Based on the results of the Cancer Cell study, the company is developing a novel test for determining the prognosis of early stage melanoma.

Functional identification of molecules
“The reported Cancer Cell findings are of great importance for Metamark and further our efforts to predict the prognosis of early stage cancers, including malignant melanoma,” said Peter Blume-Jensen, M.D., Ph.D., Chief Scientific Officer of Metamark. “This research is a concrete example of the value provided through the functional identification of molecules that play a direct role in tumor aggressiveness and supports Metamark’s founding principle that early stage tumors contain key molecular information about their progression propensity. Our next goal is to incorporate markers such as these into molecular tests that will enable the identification of patients at high risk for progression independent of traditional risk parameters, such as lymph node status and thickness of the primary lesions.”

For more Information:
Scott KL, Nogueira C, Heffernan TP, Van Doorn R, Dhakal S, et al Proinvasion Metastasis Drivers in Early-Stage Melanoma Are Oncogenes Cancer Cell (12 july 2011) 20(1) pp. 92 – 103

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