Clinicopathologic and molecular characteristics of small-scale ROS1-mutant non-small cell lung cancer (NSCLC) patients.

Background: ROS1 fusions are well treatable aberrations in NSCLC. Besides solvent-front mutations (SFM) in resistance to targeted therapy, small-scale ROS1 mutations are largely unknown. We exploratively analyzed the clinical and molecular characteristics of small-scale ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs.

Cancer care in German centers of excellence during the first 2 years of the COVID-19 pandemic.

Purpose: An increasing number of international studies demonstrate serious negative effects of the COVID-19 pandemic on the timely diagnosis of cancer and on cancer treatment. Our study aimed to quantitatively and qualitatively evaluate the capacities of German Comprehensive Cancer Centers (CCCs) in different areas of complex oncology care during the first 2 years of the COVID-19 pandemic.

Methods: Prospective panel survey over 23 rounds among 18 CCCs in Germany between March 2020 and June 2022.

Co-occurrence of targetable mutations in Non-small cell lung cancer (NSCLC) patients harboring MAP2K1 mutations.

Background: MAP2K1 mutations are rare in non-small cell lung cancer (NSCLC) and considered to be mutually exclusive from known driver mutations. Activation of the MEK1-cascade is considered pivotal in resistance to targeted therapy approaches, and MAP2K1 K57 N mutation could be linked to resistance in preclinical models. We set out this study to detect MAP2K1 mutations and potentially targetable co-mutations using a molecular multiplex approach.

Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.

The polycomb proteins BMI-1 and EZH2 are highly overexpressed by Ewing sarcoma (ES), a tumor of stem cell origin that is driven by EWS-ETS fusion oncogenes, most commonly EWS-FLI1. In the current study we analyzed expression of transcription programs that are controlled by polycomb proteins during embryonic development to determine if they are abnormal in ES. Our results show that polycomb target gene expression in ES deviates from normal tissues and stem cells and that, as expected, most targets are relatively repressed.

Modeling initiation of Ewing sarcoma in human neural crest cells.

Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC).

Self-regulatory circuits in dorsoventral axis formation of the short-germ beetle Tribolium castaneum.

The rel/NF-kappaB transcription factor Dorsal controls dorsoventral (DV) axis formation in Drosophila. A stable nuclear gradient of Dorsal directly regulates approximately 50 target genes. In Tribolium castaneum (Tc), a beetle with an ancestral type of embryogenesis, the Dorsal nuclear gradient is not stable, but rapidly shrinks and disappears.

Sog/Chordin is required for ventral-to-dorsal Dpp/BMP transport and head formation in a short germ insect.

Bone morphogenetic protein (BMP) signaling plays a major role in dorsoventral patterning in vertebrates and in Drosophila. Remarkably, in Tribolium, a beetle with an ancestral type of insect development, early BMP/dpp exhibits differential expression along the anteroposterior axis. However, the BMP/Dpp inhibitor Sog/chordin is expressed ventrally and establishes a dorsal domain of BMP/Dpp activity by transporting BMPs toward the dorsal side, like in Drosophila.