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DKTK Dresden: CRISPR/Cas9 technology to diagnose cancer mutations

No. 33c | 31/08/2016

As for many other biomedical and biotechnology disciplines, the genome scissor "CRISPR/Cas9" also opens up completely new possibilities for cancer research. Scientists of the National Center for Tumor Disease (NCT), the German Cancer Consortium (DKTK) and the Medical Faculty of the TU Dresden have shown that mutations that act as cancer drivers can be targeted and repaired. The most relevant mutations could therefore be diagnosed faster, improving personalized therapies.
The National Center for Tumor Diseases (NCT) Dresden is a joint institution of the German Cancer Research Center (DKFZ) in Heidelberg, the University Hospital Carl Gustav Carus Dresden, the Medical Faculty of the TU Dresden and the Helmholtz-Zentrum Dresden-Rossendorf. The German Cancer Consortium (DKTK) builds a strong, long-term, institutional structure between the DKFZ and universities and university hospitals all over Germany specially designated to clinical oriented cancer research.

The genome scissor CRISPR/Cas9 can help to distinguish mutations that drive cancer cell growth from mutations less relevant for cancer growth.
© Frank Buchholz, Dresden

CRISPR/Cas9 is likely one of the most revolutionary tools in biotechnology, with tremendous implications for a broad range of biological and medical disciplines. As programmable scissors this technology allows cleavage of DNA at predefined sites in the genome of cells. Now researchers from the National Center for Tumor Disease (NCT) Dresden, the German Consortium for Translational Cancer Research (DKTK) and the Medical Faculty of the TU Dresden have found a way to utilize the technology to diagnose and inactivate cancer mutations, thereby accelerating cancer research.

"Mutations in cancer cells are identified at increasing speed through next generation sequencing, but we mostly do not know, which of these mutations are actually driving the disease and which ones are rather benign " said Frank Buchholz, head of the study that appeared in the latest addition of the Journal of the National Cancer Institute (JNCI). The authors first analyzed how many of the more than 500,000 reported cancer mutations could theoretically be targeted and found that >80% of the mutations could be cleaved with the currently most popular CRISPR/Cas9 system. The research group then demonstrated that they could specifically cleave and inactivate a panel of common cancer mutations without significantly targeting the healthy, wildtype alleles. This approach enabled the researchers to unmask mutations that drive cell growth and viability in cancer cell lines. Buchholz points out: "This is an important advance, because we can now rapidly separate driver from passenger mutations. This is currently a bottleneck in cancer research. Because each cancer shows a specific combination of many mutations, this scientific approach could improve cancer diagnostics as mutations that promote cancer growth could be specifically identified. Based on the obtained results an individualized therapy could be initiated.

Gebler et al., Inactivation of cancer mutations utilizing CRISPR/Cas9. JNCI
DOI: 10.1093/jnci/djw183

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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