Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.
The American Journal of Human Genetics 99(2):337 (2016)
In ∼30% of families affected by colorectal adenomatous polyposis, no germline mutations have been identified in the previously implicated genes APC, MUTYH, POLE, POLD1, and NTHL1, although a hereditary etiology is likely. To uncover further genes with high-penetrance causative mutations, we perf...
STAT3/IRF1 Pathway Activation Sensitizes Cervical Cancer Cells to Chemotherapeutic Drugs.
Cancer Research 76(13):3872 (2016)
Neoadjuvant radio/chemotherapy regimens can markedly improve cervical cancer outcome in a subset of patients, while other patients show poor responses, but may encounter severe adverse effects. Thus, there is a strong need for predictive biomarkers to improve clinical management of cervical canc...
B-cell-specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice.
Blood 127(22):2732 (2016)
The adaptor protein MYD88 is critical for relaying activation of Toll-like receptor signaling to NF-κB activation. MYD88 mutations, particularly the p.L265P mutation, have been described in numerous distinct B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). Twenty-nine percen...
NGS-based BRCA1/2 mutation testing of high-grade serous ovarian cancer tissue: results and conclusions of the first international round robin trial.
Virchows Archiv. A. Pathological Anatomy and Hi... 468(6):697 (2016)
With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advance...
The Prosurvival IKK-Related Kinase IKKε Integrates LPS and IL17A Signaling Cascades to Promote Wnt-Dependent Tumor Development in the Intestine.
Cancer Research 76(9):2587 (2016)
Constitutive Wnt signaling promotes intestinal cell proliferation, but signals from the tumor microenvironment are also required to support cancer development. The role that signaling proteins play to establish a tumor microenvironment has not been extensively studied. Therefore, we assessed the...
PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations.
OncoImmunology 5(5):e1131379 (2016)
Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and asso...
Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma.
OncoImmunology 5(5):e1100789 (2016)
Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translat...
Oncogene and therapeutic target analyses in atypical fibroxanthomas and pleomorphic dermal sarcomas.
Oncotarget 7(16):21763 (2016)
Until now, almost nothing is known about the tumorigenesis of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Our hypothesis is that AFX is the non-infiltrating precursor lesion of PDS.
We performed the world-wide most comprehensive immunohistochemical and mutational analysis ...
Loss of the LIM-only protein Fhl2 impairs inflammatory reaction and scar formation after cardiac ischemia leading to better hemodynamic performance.
Life Sciences 151:348 (2016)
The pathogenesis of myocardial ischemia-reperfusion injury (MI/R) involves an inflammatory response. Since the four-and-a-half LIM domain-containing protein 2 (Fhl2) has been observed to modulate immune cell migration, we aimed to study the consequences of Fhl2(-/-) under MI/R with respect to im...
Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients.
Journal of Thoracic Oncology 11(1):122 (2016)
Rearrangements of RET are rare oncogenic events in patients with non-small cell lung cancer (NSCLC). While the characterization of Asian patients suggests a predominance of nonsmokers of young age in this genetically defined lung cancer subgroup, little is known about the characteristics of non-...
The impact of sequencing on diagnosis and treatment of malignant melanoma.
Expert Review of Molecular Diagnostics 16(4):423 (2016)
Melanoma is one of the clinically most important cancer types considering its high mortality rate and that it is commonly diagnosed in relatively young people. With the advent of targeted therapies and, more recently, immune checkpoint inhibitors, more treatment options are available resulting i...
Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine.
Journal of Experimental Medicine 212(12):2057 (2015)
Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is require...
Telomerase activation by genomic rearrangements in high-risk neuroblastoma.
Nature 526(7575):700 (2015)
Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their mole...
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer
Cell 162(5):1169 (2015)
FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro.
Oncotarget 6(24):20215 (2015)
Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcr...
Comprehensive genomic profiles of small cell lung cancer.
Nature 524(7563):47 (2015)
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...
Targeted next generation sequencing of parotid gland cancer uncovers genetic heterogeneity.
Oncotarget 6(20):18224 (2015)
Salivary gland cancer represents a heterogeneous group of malignant tumors. Due to their low incidence and the existence of multiple morphologically defined subtypes, these tumors are still poorly understood with regard to their molecular pathogenesis and therapeutically relevant genetic alterat...
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.
Cell 162(1):146 (2015)
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...
Serum microRNA profiles as prognostic/predictive markers in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction.
International Journal of Cancer 137(1):230 (2015)
Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis of locally advanced adenocarcinomas of the gastroesophageal junction. This study aimed to asses if serum microRNA profiles are useable as response indicators in this therapeutic setting. Fifty patients with l...
Spatial Tumor Heterogeneity in Lung Cancer with Acquired Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance: Targeting High-Level MET-Amplification and EGFR T790M Mutation Occurring at Different Sites in the Same Patient.
Journal of Thoracic Oncology 10(6):e40 (2015)