Melanoma molecular genetics
(Dr. Janine Regneri, Dr. Barbara Klotz, Brigitta Wilde, Martina Regensburger)
Malignant melanoma is one of the most dangerous tumors with an incidence rising faster than any type of cancer worldwide. Small aquarium fish, like medaka (Oryzias latipes) and different Xiphophorus species, offer valuable model systems for this disease and can be used to study melanoma initiation and progression.
Molecular mechanisms underlying melanoma development in Xiphophorus
In Xiphophorus, the development of naturally occurring melanomas can be initiated by simple crossings, which lead to a pigment cell specific overexpression of Xmrk, a mutationally activated receptor tyrosine kinase. In order to understand the molecular processes underlying the melanoma-initiating overexpression, we use Next Generation Sequencing (NGS) based approaches (RNA-seq and reduced representation bisulfite sequencing) as well as cell and molecular biology techniques, including expression pattern analyses and structural and functional promoter studies. Moreover, we are interested in the role of cdkn2ab, the fish orthologue of the human tumor suppressor genes CDKN2A and CDKN2B, for melanoma development in this model system.
Search for novel melanoma-associated genes
Our goal is to identify global melanoma associated gene expression signatures by comparing RNA expression profiles of different melanoma samples from medaka and Xiphophorus. Once identified, these signatures will be used to search for new therapeutic agents for melanoma therapy. For this purpose, we will treat melanoma-bearing fish with different chemical compounds and analyze whether they reverse the disease-associated expression signature into a healthy one using RNA-seq, NanoString technology and quantitative Realtime-PCR.
Selected references (Melanoma molecular genetics):
PLoS One (2015) 10:e0143057. Whole body melanoma transcriptome response in medaka. Schartl M, Shen Y, Maurus K, Walter R, Tomlinson C, Wilson RK, Postlethwait J, Warren WC.
Comp Biochem Physiol C Toxicol Pharmacol (2015) 178:116-27. Transcriptional control analyses of the Xiphophorus melanoma oncogene. Regneri J, Volff JN, Schartl M.
PLoS One (2012) 7:e37880. Conserved expression signatures between medaka and human pigment cell tumors. Schartl M, Kneitz S, Wilde B, Wagner T, Henkel CV, Spaink HP, Meierjohann S.
Comp Biochem Physiol C Toxicol Pharmacol (2012) 155:71-80. Expression regulation triggers oncogenicity of xmrk alleles in the Xiphophorus melanoma system. Regneri J, Schartl M.