Malignant melanoma is a disease that demonstrates a wide range of clinical behavior from relatively indolent to aggressive metastatic disease. In primary melanoma, various disease progression pathways are emerging based on DNA copy number changes in tumors, however refinement of these subtypes is required for biological interpretation.
Our own studies of disseminated melanoma reveals a division into four discrete gene expression entities that are significantly correlated to clinical outcome. Interestingly, an elevated immune reaction in tumors is suggested to correlate with better survival. These are welcome findings in a disease characterized by consistent resistance to current chemotherapy regimes and where novel treatment strategies are urgently needed. Our research includes validation of these results and more in-depth genetic analyses using next-generation sequencing. Genomic results will subsequently be integrated with functional and treatment-response studies to determine optimal treatment based on molecular subclass. In primary melanoma a similar picture is emerging where immune response and proliferation are two key molecular determinants of clinical outcome. Using DASL analysis (gene expression profiling on FFPE RNA) we are also performing a molecular screen of primary melanoma where preliminary results indicate distinct expression patterns in melanomas from predisposed individuals as well as melanomas from patients with an improved survival.
In an international collaboration we are also increasing efforts to identify susceptibility genes that predispose carriers for the rare ocular melanomas, but which will also shed light on development of cutaneous malignant melanoma, which co-segregates with ocular melanoma in the large pedigrees.
Taken together, we believe that a translational research approach in melanoma will be a valuable tool for future design and considerations in clinical trials but will also provide prognostic and diagnostic advantages.
Page Manager: Göran Jönsson
Last modified: 2011-08-17
Göran Jönsson, Ph.D.
Head, Melanoma Genomics Unit
Asst. Professor, Div. of Oncology
Phone: +46 46 2221444
E-mail: goran_b.jonsson@med.lu.se
