Researchers of the University of Geneva (UNIGE), the Ludwig Center for Cancer Research of the University of Lausanne, the Cantonal University Hospital (CHUV), and the Swiss Institute of Bioinformatics (SIB) have identified novel mutationsin the genes MEK1 and MEK2 that are involved in the development of melanoma. These findings, which open new perspectives to personalized treatments, were recently published in the journal Nature Genetics.
Malignant melanoma is a highly aggressive skin tumor that is mostly resistant to conventional chemotherapy and has a high mortality rate. In Switzerland, melanoma accounts for about 5% of all new cancers (Swiss National Institute for Cancer Epidemiology and Registration). The development of novel therapies against melanoma is a long-standing research priority for the Institutions involved in the study.
Skin exposure to UV light is the predominant environmental driver in melanoma leading to the accumulation of genomic mutations and resulting in deregulation of mechanisms controlling cell growth, proliferation and survival. Half of all melanomas harbor an oncogenic mutation in the BRAF gene. Patients carrying this mutation can benefit from a newly developed drug that has been approved for use in the U.S. and Switzerland. However, it is thought that mutations in additional unknown genes contribute to the abnormal growth of skin cells in patients with melanoma.
To look for additional gene mutations, scientists from UNIGE, LICR, CHUV and SIB teamed up to analyze the genomes of melanoma samples. This two-year collaborative study was funded by LICR in the context of its Melanoma Initiative and by an SNF National Centers of Competence in Research grant to UNIGE, Frontiers in Genetics.
The results of this study revealed several novel genes that may contribute to the development of melanomas when mutated, the most notable of which are MEK1 and MEK2. The proteins produced by these genes act in the same cell signaling pathway as BRAF and regulate cellular processes, such as proliferation and migration. The mutations make the proteins over-reactive.
The finding of MEK1/2 mutations, detected in 8% of melanomas, opens new perspectives in the treatment strategies of this cancer. “Today there are drugs under investigation in clinical trials that are inhibiting MEK1/2 activity and more powerful novel compounds are under development. We are hopeful that the results of this study will help to better design the appropriate treatments for melanoma patients,” comments Donata Rimoldi, one of the leading authors and researcher at LICR.
“These findings are the result of a fruitful collaboration between genome analysts, cell biologists, geneticists, computational biologists and clinical scientists who exploited the most up-to-date methodologies of genomic exploration and computational analysis », explains Stylianos Antonarakis, senior author of the article and professor of Genetics at UNIGE.