In a new study published in Nature Medicine researchers lead by Cédric Blanpain, WELBIO Investigator at ULB, describe the genetic abnormalities leading to the development, progression and metastasis of mouse skin squamous cell carcinoma (SCC) and demonstrate interesting similarities with human cancers.
SCC of the skin is one of the most frequent cancers in humans affecting more than half million new persons every year in the world. The transformation of a normal cell to a cancer cell is caused by an accumulation of genetic abnormalities in the progeny of single cells. The spectrum of genetic anomalies found in a variety of human cancers have been described. SCC arising from various organs including head-and-neck, lung, esophagus and skin, are induced by carcinogens, such as tobacco and UV exposure. Mouse models of carcinogen-induced skin SCCs have been used since a century and became the most extensively used model to study cancer in vivo. However, it is still unclear whether mouse carcinogen-induced skin SCCs is mediated by the same spectrum of mutations as found in human cancer
The scientists used a mouse model of skin SCC induced by a chemical carcinogen, which is the most frequently used mouse model in cancer research, and studied the genetic abnormalities in premalignant and fully malignant tumors, as well as their metastases. Using state-of-the-art high throughput sequencing technologies (known as “next generation sequencing” or NGS), they define the entire landscape of mutations (both point mutations as well as chromosome amplifications and deletions) that lead to mouse skin cancer formation and progression.
By analyzing the genetic abnormalities that accompanied the progression from a benign tumor to fully malignant and invasive tumors, Nassar and colleagues found that tumor progression was not accompanied by additional point mutations but rather by larger chromosomal copy number alterations, leading to the amplification or deletion of important genes controlling tumor formation. Finally, by reconstructing the lineage tree of primary cancers and their metastasis, the authors demonstrate that very few additional mutations were found in metastasis, suggesting that metastasis could be regulated by other additional non-genetic mechanisms.
Dany Nassar et al, Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma.¬ Nature Medicine (2015) doi:10.1038/nm.3878