1. NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas.

    International Journal of Cancer 138(4):927 (2016) PMID 26340530 PMCID PMC4832386

    Small cell lung cancers (SCLCs) and extrapulmonary small cell cancers (SCCs) are very aggressive tumors arising de novo as primary small cell cancer with characteristic genetic lesions in RB1 and TP53. Based on murine models, neuroendocrine stem cells of the terminal bronchioli have been postula...
  2. Implementing amplicon-based next generation sequencing in the diagnosis of small cell lung carcinoma metastases.

    Experimental and Molecular Pathology 99(3):682 (2015) PMID 26546837

    Small cell lung carcinoma (SCLC) is the most aggressive entity of lung cancer. Rapid cancer progression and early formation of systemic metastases drive the deadly outcome of SCLC. Recent advances in identifying oncogenes by cancer whole genome sequencing improved the understanding of SCLC carci...
  3. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer

    Cell 162(5):1169 (2015)

  4. Comprehensive genomic profiles of small cell lung cancer.
    Julie George, Jing Shan Lim, Se Jin Jang, Yupeng Cun, Luka Ozretić, Gu Kong, Frauke Leenders, Xin Lu, Lynnette Fernández-Cuesta, Graziella Bosco, Christian Müller, Ilona Dahmen, Nadine S Jahchan, Kwon-Sik Park, Dian Yang, Anthony N Karnezis, Dedeepya Vaka, Angela Torres, Maia Segura Wang, Jan O Korbel, Roopika Menon, Sung-Min Chun, Deokhoon Kim, Matt Wilkerson, Neil Hayes, David Engelmann, Brigitte Pützer, Marc Bos, Sebastian Michels, Ignacija Vlasic, Danila Seidel, Berit Pinther, Philipp Schaub, Christian Becker, Janine Altmüller, Jun Yokota, Takashi Kohno, Reika Iwakawa, Koji Tsuta, Masayuki Noguchi, Thomas Muley, Hans Hoffmann, Philipp A Schnabel, Iver Petersen, Yuan Chen, Alex Soltermann, Verena Tischler, Chang-min Choi, Yong-Hee Kim, Pierre Massion, Yong Zou, Dragana Jovanovic, Milica Kontic, Gavin M Wright, Prudence A Russell, Benjamin Solomon, Ina Koch, Michael Lindner, Lucia A Muscarella, Annamaria la Torre, John K Field, Marko Jakopovic, Jelena Knezevic, Esmeralda Castaños-Vélez, Luca Roz, Ugo Pastorino, Odd-Terje Brustugun, Marius Lund-Iversen, Erik Thunnissen, Jens Köhler, Martin Schuler, Johan Botling, Martin Sandelin, Montserrat Sanchez-Cespedes, Helga B Salvesen, Viktor Achter, Ulrich Lang, Magdalena Bogus, Peter M Schneider, Thomas Zander, Sascha Ansén, Michael Hallek, Jürgen Wolf, Martin Vingron, Yasushi Yatabe, William D Travis, Peter Nürnberg, Christian Reinhardt, Sven Perner, Lukas Heukamp, Reinhard Büttner, Stefan A Haas, Elisabeth Brambilla, Martin Peifer, Julien Sage, and Roman K Thomas

    Nature 524(7563):47 (2015) PMID 26168399 PMCID PMC4861069

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis...
  5. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

    Cell 162(1):146 (2015) PMID 26140595

    KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
  6. The histone code reader SPIN1 controls RET signaling in liposarcoma.

    Oncotarget 6(7):4773 (2015) PMID 25749382 PMCID PMC4467114

    The histone code reader Spindlin1 (SPIN1) has been implicated in tumorigenesis and tumor growth, but the underlying molecular mechanisms remain poorly understood. Here, we show that reducing SPIN1 levels strongly impairs proliferation and increases apoptosis of liposarcoma cells in vitro and in ...
  7. PD-L1 expression in small cell neuroendocrine carcinomas.

    European Journal of Cancer 51(3):421 (2015) PMID 25582496

    Small cell lung cancer and extrapulmonary small cell carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD-L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. ...
  8. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer.

    Nature Medicine 20(9):1027 (2014) PMID 25173427 PMCID PMC4159407

    Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising...
  9. Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.

    Nature Communications 5:3518 (2014) PMID 24670920 PMCID PMC4132974

    Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmo...
  10. A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation.

    Genes & Development 26(8):797 (2012) PMID 22465951 PMCID PMC3337454

    The linker histone H1 is a key player in chromatin organization, yet our understanding of the regulation of H1 functions by post-translational modifications is very limited. We provide here the first functional characterization of H1 acetylation. We show that H1.4K34 acetylation (H1.4K34ac) is m...
  11. The role of molecular diagnostics in cancer diagnosis and treatment.

    Onkologie 35 Suppl 1:8 (2012) PMID 22286582

    The field of molecular diagnostics has improved our understanding of the pathophysiological mechanisms of malignant alteration, especially in lung cancer which remains the leading cause of cancer-related mortality worldwide. The role of the epidermal growth factor receptor (EGFR) and other molec...
  12. High nuclear poly(adenosine diphosphate-ribose) polymerase expression is predictive for BRCA1- and BRCA2-deficient breast cancer.

    Journal of Clinical Oncology 29(34):4586 (2011) PMID 22025145

  13. Late life depression: challenge or curse for the general practitioner (GP). A cohort study.

    Archives of Gerontology and Geriatrics 52(3):e134 (2011) PMID 20933289

    The aim of this study was to examine specificity of GP's care for elderly depressed patients. Among 17,000 examinees (10 GP-Offices) were extracted 231 patients with diagnosis of depressive episode (F32) and 152 with diagnosis of recurrent depressive disorder (F33) classified according to ICD-10...