Thomas Lab
Translational Genomics
Cancer is a disease of the genome; genetic lesions (gene mutations, gene copy number changes, structural genetic changes, etc.) lead to irreversible changes in the intracellular signal transduction pathways that the tumor cells become dependent upon. A new class of cancer therapeutics targeting specific signaling pathways activated by genetic lesions has shown clinical success. Understanding the dependency associated with each genetic alteration is crucial in order to device specific inhibitory strategies to interfere with the activity of the respective oncogene or the pathways activated downstream of the oncogene. Such preclinical work can help expediting the preclinical-to-clinical transition of novel cancer therapeutics and to make them more effective. Similarly, linking drug response and clinical features of patients to genetic alterations is essential for a continuous re-assessment of the validity of such preclinical predictions.
Our research focus:
Our lab has a focus on analyzing understudied subtypes of lung cancer, including squamous-cell carcinoma and small-cell carcinoma (SCLC). The development of novel high-throughput genome analysis technologies has enabled the detection of alterations in the genomes of tumor cells at single-base resolution and in ‘real-time’. Genome alterations lead to irreversible changes in intracellular signal transduction pathways that the tumor cells become dependent upon. Understanding these genomic events as well as their impact on cellular signal transduction pathways is a crucial prerequisite to the development of novel therapeutic strategies for fighting cancer.
Our goals:
We seek to identify genome alterations that permit selecting patients for personalized cancer therapy. Such alterations can enable treatment with higher efficacy and reduced toxicity.
Our approach:
Our laboratory has created a conceptual framework as well as methodological strategies for approaching these needs. We have developed an international network for cancer genome analyses and we have developed a platform for functional cell biology analysis of the novel mutations that we discover. We have successfully applied this two-pronged approach to the discovery of cancer genotypes that may be connected with drug response.
Principal Investigator
Univ. Prof. Dr. med. Roman Thomas
Director of the Department of Translational Genomics
Team
Most important publications
George J, Walter V, Peifer M, Alexandrov LB, Seidel D, Leenders F, Maas L, Müller C, Dahmen I, Delhomme TM, Ardin M, Leblay N, Byrnes G, Sun R, De Reynies A, McLeer-Florin A, Bosco G, Malchers F, Menon R, Altmüller J, Becker C, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soloway MG, Wilkerson MD, Cun Y, McKay JD, Moro-Sibilot D, Brambilla CG, Lantuejoul S, Lemaitre N, Soltermann A, Weder W, Tischler V, Brustugun OT, Lund-Iversen M, Helland Å, Solberg S, Ansén S, Wright G, Solomon B, Roz L, Pastorino U, Petersen I, Clement JH, Sänger J, Wolf J, Vingron M, Zander T, Perner S, Travis WD, Haas SA, Olivier M, Foll M, Büttner R, Hayes DN, Brambilla E, Fernandez-Cuesta L, Thomas RK. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat Commun. 2018 Mar 13;9(1):1048
Drapkin BJ, George J, Christensen CL, Mino-Kenudson M, Dries R, Sundaresan T, Phat S, Myers DT, Zhong J, Igo P, Hazar-Rethinam MH, Licausi JA, Gomez-Caraballo M, Kem M, Jani KN, Azimi R, Abedpour N, Menon R, Lakis S, Heist RS, Büttner R, Haas S, Sequist LV, Shaw AT, Wong KK, Hata AN, Toner M, Maheswaran S, Haber DA, Peifer M, Dyson N, Thomas RK, Farago AF. Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts. Cancer Discov. 2018 May;8(5):600-615
Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Krämer A, Roncaioli JL, Sand F, Heuckmann JM, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmüller J, Nürnberg P, Thierry-Mieg J, Thierry-Mieg D, Mariappan A, Heynck S, Mariotti E, Henrich KO, Glöckner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Höfer T, Achter V, Lang U, Theissen J, Volland R, Saadati M, Eggert A, de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Büttner R, Perner S, Hero B, Schramm A, Schulte JH, Herrmann C, O'Sullivan RJ, Westermann F, Thomas RK, Fischer M. (co-corresponding author). Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015 Oct 14. doi: 10.1038/nature14980.
George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernández-Cuesta L, Bosco G, Müller C, Dahmen I, Jahchan NS, Park KS, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun SM, Kim D, Wilkerson M, Hayes N, Engelmann D, Pützer P, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Janine Altmüller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Yuan Chen Y, Soltermann A, Tischler V, Choi CM, Kim YH, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knezevic J, Castaños-Vélez E, Roz L, Pastorino U, Brustugun OT, Lund-Iversen M, Thunnissen E, Köhler K, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Ulrich Lang U, Bogus M, Schneider PM, Zander T, Ansén S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nürnberg P, Reinhardt C, Perner S, Heukamp L, Büttner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015 Aug 6;524(7563):47-53.
Fernandez-Cuesta L, Peifer M, Lu X, Sun R, Ozretić L, Seidel D, Zander T, Leenders F, George J, Müller C, Dahmen I, Pinther B, Bosco G, Konrad K, Altmüller J, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soltermann A, Brustugun OT, Helland Å, Solberg S, Lund-Iversen M, Ansén S, Stoelben E, Wright GM, Russell P, Wainer Z, Solomon B, Field JK, Hyde R, Davies MP, Heukamp LC, Petersen I, Perner S, Lovly CM, Cappuzzo F, Travis WD, Wolf J, Vingron M, Brambilla E, Haas SA, Buettner R, Thomas RK. Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat Commun. 2014 Mar 27;5:3518.
Fernandez-Cuesta L, Plenker D, Osada H, Sun R, Menon R, Leenders F, Ortiz-Cuaran S, Peifer M, Bos M, Dabler J, Malchers F, Schottle J, Vogel W, Dahmen I, Koker M, Ullrich RT, Wright GM, Russell PA, Wainer Z, Solomon B, Brambilla E, Nagy-Mignotte H, Moro-Sibilot D, Brambilla CG, Lantuejoul S, Altmuller J, Becker C, Nurnberg P, Heuckmann JM, Stoelben E, Petersen I, Clement JH, Sanger J, Muscarella LA, la Torre A, Fazio VM, Lahortiga I, Perera T, Ogata S, Parade M, Brehmer D, Vingron M, Heukamp LC, Buettner R, Zander T, Wolf J, Perner S, Ansen S, Haas SA, Yatabe Y, Thomas RK. CD74-NRG1 fusions in lung adenocarcinoma. Cancer Discov. 2014 Apr;4(4):415-22.
Clinical Lung Cancer Genome Project (CLCGP) and Network Genomic Medicine (NGM). Thomas RK (last author). A genomics based classification of Human lung tumors. Sci Tranl Med. 2013 Oct 30; 5(209): 209ra153
Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Müller C, Di Cerbo V, Schildhaus HU, Altmüller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Böhm D, Ansén S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grütter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sänger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Büttner R, Wolf J, Nürnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, and Thomas RK. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012 Oct;44(10):1104-10.
Sos ML, Dietlein F, Peifer M, Schöttle J, Balke-Want H, Müller C, Koker M, Richters A, Heynck S, Malchers F, Heuckmann JM, Seidel D, Eyers PA, Ullrich RT, Antonchick AP, Vintonyak VV, Schneider PM, Ninomiya T, Waldmann H, Büttner R, Rauh D, Heukamp LC, and Thomas RK. A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc Natl Acad Sci USA. 2012 Oct 16;109(42):17034-9
- Thomas RK, Baker AC, DeBiasi RM, Winckler W, LaFramboise T, Lin WM, Feng W, Wang M, MacConnaill LE, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar AF, Minna J, Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA, Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD, Dummer R, Wagner S, Herlyn M, Sellers WR, Meyerson M and Garraway LA. High-throughput oncogene mutation profiling in human cancer. Nat Genet, 2007 Mar;39(3):347-351.