Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer.

The discovery of frequent 8p11-p12 amplifications in squamous cell lung cancer (SQLC) has fueled hopes that FGFR1, located inside this amplicon, might be a therapeutic target. In a clinical trial, only 11% of patients with 8p11 amplification (detected by FISH) responded to FGFR kinase inhibitor treatment. To understand the mechanism of FGFR1 dependency, we performed deep genomic characterization of 52 SQLCs with 8p11-p12 amplification, including 10 tumors obtained from patients who had been treated with FGFR inhibitors.

MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition.

Introduction: MET fusions have been described only rarely in NSCLC. Thus, data on patient characteristics and treatment response are limited. We here report histopathologic data, patient demographics, and treatment outcome including response to MET tyrosine kinase inhibitor (TKI) therapy in MET fusion-positive NSCLC.

Resistance to MET inhibition in MET-dependent NSCLC and therapeutic activity after switching from type I to type II MET inhibitors.

Objectives: Resistance to MET inhibition occurs inevitably in MET-dependent non-small cell lung cancer and the underlying mechanisms are insufficiently understood. We describe resistance mechanisms in patients with MET exon 14 skipping mutation (METΔ), MET amplification, and MET fusion and report treatment outcomes after switching therapy from type I to type II MET inhibitors.

Materials And Methods: Pre- and post-treatment biopsies were analysed by NGS (next generation sequencing), digital droplet PCR (polymerase chain reaction), and FISH (fluorescense in situ hybridization).

Mismatch Repair Deficiency and Somatic Mutations in Human Sinonasal Tumors.

Due to limitations in local therapy approaches for sinonasal tumors, improvement in systemic therapies plays a pivotal role for prolongation of the patient's survival. The aim of this study was to examine potential biomarkers, including deficiency in mismatch repair proteins (dMMR)/microsatellite instability (MSI-H) in sinonasal cancers and their precancerous lesions. A comprehensive analysis of 10 sinonasal cancer cell lines by whole exome sequencing, screening 174 sinonasal tumors by immunohistochemistry (IHC) for mismatch repair deficiency and next generation sequencing (NGS) of 136 tumor samples revealed a dMMR/MSI-H sinonasal squamous cell carcinoma (SNSCC) cell line based on a somatic missense mutation in and an overall frequency of dMMR/MSI-H SNSCC of 3.

Detection of gene fusions using targeted next-generation sequencing: a comparative evaluation.

Background: Gene fusions represent promising targets for cancer therapy in lung cancer. Reliable detection of multiple gene fusions is therefore essential.

Methods: Five commercially available parallel sequencing assays were evaluated for their ability to detect gene fusions in eight cell lines and 18 FFPE tissue samples carrying a variety of known gene fusions.

Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing.

Outcome of immune checkpoint inhibition in cancer can be predicted by measuring PDL1 expression of tumor cells. Search for additional biomarkers led to tumor mutational burden (TMB) as surrogate marker for neoantigens presented. While TMB was previously determined via whole exome sequencing (WES), there have been approaches with comprehensive gene panels as well.

Comparison of in Situ and Extraction-Based Methods for the Detection of ROS1 Rearrangements in Solid Tumors.

Clinical data confirmed that patients with ROS1 rearrangement are sensitive to specific inhibitors. Therefore, reliable detection of ROS1 rearrangements is essential. Several diagnostic techniques are currently available.

Copy number variations in atypical fibroxanthomas and pleomorphic dermal sarcomas.

Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are frequent cutaneous sarcomas typically arising on sun-exposed skin in elderly patients. In contrast to AFX, which generally do not recur after complete excision, PDS locally recur in up to 50% and metastasize in up to 20%. We recently detected characteristic UV-induced mutations as potential driver mutation in almost all PDS investigated as well as activating and gene mutations in around one third of our tumors representing targets for personalized treatments in patients with unresectable or metastasized PDS.

Caspase-8, association with Alzheimer's Disease and functional analysis of rare variants.

The accumulation of amyloid beta (Aβ) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.

Molecular convergence of the parasitic plant species Cuscuta reflexa and Phelipanche aegyptiaca.

The parasitic plant species Cuscuta reflexa and Phelipanche aegyptiaca have independently developed parasitism, the former parasitizing on shoots and the latter attaching to roots. Regardless of these differences, the two species use similar organs, termed haustoria, to attach to the host plant. In this study, we show that this morphological similarity can be extended to the molecular level.