NGFN-PLUS
Systematic high-throughput analysis of oncogenicity of human oncogene mutations
| Coordinator: | Prof. Dr. Roman Thomas | |
| Institution: | Abteilung Translationale Genomik, Universität zu Köln | |
| Homepage: | www.translational-genomics.uni-koeln.de |
Focus of this sub-project was the systematic analysis of oncogene mutations and the resulting dependence of downstream signaling pathways of tumors in a cellular system.
Within the scope of the project we performed extensive genotype-phenotype studies in lung tumors to establish genetic signatures for the prediction of therapeutic intervention (Sos et al, J Clin Invest., 2009). Moreover, we could identify a new, clinically relevant mechanism of resistance to the EGFR inhibitor erlotinib in non-small cell lung cancer (SCLC) (Sos et al, Cancer Res, 2010) and we could proof that tumors with genetic alterations in receptor tyrosine kinases are dependent on the Pi3- kinase pathway (Sos et al, PNAS 2009).
As part of the Clinical Lung Cancer Project (CLCGP), which was initiated as part of the NGFN network, we collected over 1500 samples worldwide with clinical data to subsequently characterize them genomically. The results of the whole-genome sequencing of SCLC showed an extremely high mutation rate compared to other types of lung cancer (Peifer et al., Nature Genetics, 2012). In addition, we could identify individual mutated genes, which are critical for tumor growth. Moreover, two novel discoveries, the DDR2 and FGFR1 mutations in squamous cell carcinoma were already transferred into clinical studies (Weiss et al, Sci Transl Med 2010 Hammerman et al., Cancer Discovery 2011).
With the help of next generation sequencing technology, we developed a diagnostic tool to detect mutations, rearrangements and copy number changes in tumor samples in a single analysis (Querings et al., Plos One, 2011). Through close collaboration with the Network Genomic Medicine (NGM) at the Center for Integrated Oncology Cologne-Bonn (CIO), this method is already used in routine diagnostics to determine tumor mutations in cancer patients and to provide a personalized cancer therapy. In cooperation with our project partners we could in total contribute to the improvement of treatment strategies of cancer patients and to the development of new targeted therapies and diagnostic methods.
Within the scope of the project we performed extensive genotype-phenotype studies in lung tumors to establish genetic signatures for the prediction of therapeutic intervention (Sos et al, J Clin Invest., 2009). Moreover, we could identify a new, clinically relevant mechanism of resistance to the EGFR inhibitor erlotinib in non-small cell lung cancer (SCLC) (Sos et al, Cancer Res, 2010) and we could proof that tumors with genetic alterations in receptor tyrosine kinases are dependent on the Pi3- kinase pathway (Sos et al, PNAS 2009).
As part of the Clinical Lung Cancer Project (CLCGP), which was initiated as part of the NGFN network, we collected over 1500 samples worldwide with clinical data to subsequently characterize them genomically. The results of the whole-genome sequencing of SCLC showed an extremely high mutation rate compared to other types of lung cancer (Peifer et al., Nature Genetics, 2012). In addition, we could identify individual mutated genes, which are critical for tumor growth. Moreover, two novel discoveries, the DDR2 and FGFR1 mutations in squamous cell carcinoma were already transferred into clinical studies (Weiss et al, Sci Transl Med 2010 Hammerman et al., Cancer Discovery 2011).
With the help of next generation sequencing technology, we developed a diagnostic tool to detect mutations, rearrangements and copy number changes in tumor samples in a single analysis (Querings et al., Plos One, 2011). Through close collaboration with the Network Genomic Medicine (NGM) at the Center for Integrated Oncology Cologne-Bonn (CIO), this method is already used in routine diagnostics to determine tumor mutations in cancer patients and to provide a personalized cancer therapy. In cooperation with our project partners we could in total contribute to the improvement of treatment strategies of cancer patients and to the development of new targeted therapies and diagnostic methods.
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