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Breakthrough in liver cancer

29. September 2014. A multidisciplinary, international team led by C. Kubisch (Ulm University), K. Ramadan (Oxford University), J. Terzic (Split University), D. Amor (University of Melbourne) and I. Dikic (Goethe University in Frankfurt) reports in today's online issue of Nature Genetics the discovery of a hitherto unknown mutation causing early onset liver cancer.

Individuals carrying this mutation are highly likely to develop liver cancer during childhood, and also show multiple signs of premature aging. The mutation disrupts the function of a gene called SPRTN, resulting in accumulation of DNA damage during each cell division and subsequent chromosome instability. It is the first time that mutations in this gene have been linked to liver cancer, and this opens the avenue for follow-up studies regarding the role of this gene in tumour development in general, and liver cancers specifically. Despite being the third leading cause of cancer deaths worldwide, with many risk factors like hepatitis infection or alcohol abuse being well known, the molecular pathogenesis of liver cancer has remained largely elusive. Therefore, the finding reported in Nature Genetics represents a major milestone in understanding the molecular details of tumour development in the liver, and could lead to new therapeutic and diagnostic approaches.

Ivan Dikic comments: “This is an excellent example of success of long term projects. It started more than 7 years ago, at the time focusing on Ub-dependent DNA repair pathways. Later, by serendipity, the results turned out to be critical for understanding the development of hepatocarcinoma. The project has attracted several collaborators around the world and only by closely collaborating we were able to successfully accomplish this task. It also shows why a certain stamina on the side of fund providers (7 years without a single publication) is essential for addressing big and important questions in biomedicine.”

Ivan Dikic
Institute of Biochemistry II
Goethe University Frankfurt
Frankfurt (Main), Germany
Tel.: +49 (0)69 6301-5964

Full reference:
Lessel D, Vaz B, Halder S, Lockhart PJ, Marinovic-Terzic I, Lopez-Mosqueda J, Philipp M, Sim JCH, Smith KR, Oehler J, Cabrera E, Freire R, Pope K, Nahid A, Norris F, Leventer RJ, Delatycki MB, Barbi G, Ameln vS, Högel J, Degoricija M, Fertig R, Burkhalter MD, Hofmann K, Thiele H, Altmüller J, Nürnberg G, Nürnberg P, Bahlo M, Martin GM, Aalfs CM, Oshima J, Terzic J, Amor DJ, Dikic I, Ramadan K, Kubisch C (2014) Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. Nat Genet doi:10.1038/ng.3103 More...