Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases.

Objectives: In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM).

Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey.

There is increasing evidence that therapy-related acute lymphoblastic leukemia (trALL) resulting from chemo- and/or radiotherapy represents a distinct entity. However, apart from rearrangements, which have been repeatedly reported in this subgroup, the relevance of other aberrations remains controversial due to divergent study results and sparse molecular analyses. Within our ALL patient cohort, 15% ( = 19/131) met the criteria for trALL with a high proportion of Ph + and rearrangements.

Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype.

Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8 T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8 T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules.

Improving the turnaround time of molecular profiling for advanced non-small cell lung cancer: Outcome of a new algorithm integrating multiple approaches.

Background: Molecular tumor profiling to identify oncogenic drivers and actionable mutations has a profound impact on how lung cancer is treated. Especially in the subgroup of non-small cell lung cancer (NSCLC), molecular testing for certain mutations is crucial in daily clinical practice and is recommended by international guidelines. To date, a standardized approach to identify druggable genetic alterations are lacking.

Mutational Landscape and Expression of PD-L1 in Patients with Non-Small Cell Lung Cancer Harboring Genomic Alterations of the MET gene.

Background: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutations and MET gene amplification occur in 3-5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) targeting MET alterations have shown promising results in these patients.

Objective: The aim of this study was to describe the genomic profile, PD-L1 expression and clinicopathological features of MET dysregulated NSCLC.

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.

c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC.

Molecular and immunophenotypic characterization of SMARCB1 (INI1) - deficient intrathoracic Neoplasms.

The switch/sucrose-non-fermenting (SWI/SNF) complex is an ATP-dependent chromatin remodeling complex that plays important roles in DNA repair, transcription and cell differentiation. This complex consists of multiple subunits and is of particular interest in thoracic malignancies due to frequent subunit alteration of SMARCA4 (BRG1). Much less is known about SMARCB1 (INI1) deficient intrathoracic neoplasms, which are rare, often misclassified and understudied.

Targeting ALK in Neuroendocrine Tumors of the Lung.

Background: () rearrangements are known oncogenic drivers in non-small cell lung cancer (NSCLC). Few case reports described the occurrence of such rearrangements in large cell neuroendocrine carcinomas (LCNECs) of the lung without information on clinical responses to ALK tyrosine kinase inhibitors (TKIs) in these cases. Currently, neuroendocrine tumors of the lungs are not screened for rearrangements.

Comprehensive Validation of Diagnostic Next-Generation Sequencing Panels for Acute Myeloid Leukemia Patients.

Next-generation sequencing has greatly advanced the molecular diagnostics of malignant hematological diseases and provides useful information for clinical decision making. Studies have shown that certain mutations are associated with prognosis and have a direct impact on treatment of affected patients. Therefore, reliable detection of pathogenic variants is critically important.

Histologic and Molecular Patterns in Responders and Non-responders With Chronic-Active Antibody-Mediated Rejection in Kidney Transplants.

Introduction: There is no proven therapy for chronic-active antibody-mediated rejection (caABMR), the major cause of late kidney allograft failure. Histological and molecular patterns associated with possible therapy responsiveness are not known.

Methods: Based on rigorous selection criteria this single center, retrospective study identified 16 out of 1027 consecutive kidney transplant biopsies taken between 2008 and 2016 with pure, unquestionable caABMR, without other pathologic features.

A functional approach towards the design, development, and test of an affordable dynamic prosthetic foot.

Humanitarian actors involved in physical rehabilitation, such as the International Committee of the Red Cross (ICRC), usually provide their beneficiaries with lower-limb prostheses comprising Solid Ankle Cushion Heel (SACH) feet as these are considered appropriate (price, durability, low profile to fit a majority of patients, appearance) and reliable for all ambulation levels. However, individuals in low-resource settings having higher ambulation abilities would greatly benefit from dynamic prosthetic feet with improved biomechanics and energy storage and release. Some attempts tried to address this increasing need (e.

Eosinophilic solid and cystic renal cell carcinoma and renal cell carcinomas with TFEB alterations: a comparative study.

Aims: Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently described renal tumour entity with frequent cytokeratin (CK)20 positivity, commonly harbouring TSC mutations. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB-amplified RCC and TFEB-translocated RCC, which frequently express Melan A. Herein, we provide a comparative analysis of six ESC RCC with four TFEB-amplified/translocated RCC.

Setting a diagnostic benchmark for tumor BRCA testing: detection of BRCA1 and BRCA2 large genomic rearrangements in FFPE tissue - A pilot study.

PARP inhibitors are used for treatment of tumors lacking function of the double-strand DNA break repair proteins BRCA1 or BRCA2 and are already approved for several cancer types. Thus, it is clinically crucial to determine germline as well as somatic BRCA1/2 mutations in those patients. The amplicon-based Oncomine BRCA1 and BRCA2 Assay is a test routinely used in diagnostics with FFPE specimens.

The Role of the Liquid Biopsy in Decision-Making for Patients with Non-Small Cell Lung Cancer.

Liquid biopsy is a rapidly emerging tool of precision oncology enabling minimally invasive molecular diagnostics and longitudinal monitoring of treatment response. For the clinical management of advanced stage lung cancer patients, detection and quantification of circulating tumor DNA (ctDNA) is now widely adopted into clinical practice. Still, interpretation of results and validation of ctDNA-based treatment decisions remain challenging.

Real-World Treatment Patterns and Survival Outcome in Advanced Anaplastic Lymphoma Kinase (ALK) Rearranged Non-Small-Cell Lung Cancer Patients.

Survival of ALK-rearranged NSCLC patients has dramatically improved by the use of multiple ALK-tyrosine kinase inhibitors (ALK-TKI). However, still little is known about the impact of drug sequencing and clinical features on survival in a real-world setting. Patients with stage IV ALK-rearranged NSCLC treated at six centers in Switzerland and Italy were identified and standard clinical variables collected.

Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.

Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies.

Multicenter Evaluation of the Fully Automated PCR-Based Idylla EGFR Mutation Assay on Formalin-Fixed, Paraffin-Embedded Tissue of Human Lung Cancer.

Before initiating treatment of advanced non-small-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.

Oncogenic driver mutations in Swiss never smoker patients with lung adenocarcinoma and correlation with clinicopathologic characteristics and outcome.

Purpose: Lung cancer in never smokers is recognized as a distinct molecular, clinicopathologic and epidemiologic entity. The aim of the study was to investigate the molecular profile in Swiss never smokers with lung adenocarcinoma and to correlate the mutation status with clinicopathologic and demographic patient characteristics and outcome.

Methods: One hundred thirty-eight never smokers diagnosed with lung adenocarcinoma at the University Hospital Zurich between 2011-2018 were included in the study.

New Insights into Tumor Heterogeneity: A Case of Solid-Oncocytic Epithelial-Myoepithelial Carcinoma of the Parotid Gland Harboring a HRAS and Heterogeneous Terminating ARID1A Mutation.

Epithelial-myoepithelial carcinoma (EMC) can be a challenging diagnosis due to a lack of obvious invasion and bland cytology. We report an unusual case of a low-grade EMC with prominent fibrous stroma, an extensive solid-oncocytic differentiation and limited areas of morphological clearly identifiable characteristic biphasic (tubular) differentiation, clear cells and PAS-positive secretions/calcifications. Both areas were investigated by next generation sequencing (Oncomine comprehensive assay) and revealed a typical concordant HRAS p.

Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma.

Background: Extensive DNA sequencing has led to an unprecedented view of the diversity of individual genomes and their evolution among patients with clear cell renal cell carcinoma (ccRCC).

Objective: To understand subclonal architecture and dynamics of patient-derived two-dimensional (2D) and three-dimensional (3D) ccRCC models in vitro, in order to determine whether they mirror ccRCC inter- and intratumor heterogeneity.

Design, Setting, And Participants: We have established a comprehensive platform of living renal cancer cell models from ccRCC surgical specimens.

Melanoma patients with additional primary cancers: a single-center retrospective analysis.

Recent progress in the diagnosis and treatment of primary and metastatic cutaneous melanoma (CM) has led to a significant increase in the patients` expectancy of life. The development of additional primary tumors (APT) other than CM represents an important survival issue. Of a total of 1764 CM patients, 80 (4.

Microfluidic-Based Immunohistochemistry Combined With Next-Generation Sequencing on Diagnostic Tissue Sections for Detection of Tumoral BRAF V600E Mutation.

Objectives: Tailored diagnostics requires immunohistochemistry (IHC) and next generation sequencing (NGS). Here we combined on a single paraffin-embedded slide microfluidic-based IHC (micro-IHC) and NGS for BRAF V600E mutation detection in BRAFomas.

Methods: For micro-IHC, we performed the primary antibody incubation step of conventional chromogenic IHC in a LabSat device (Lunaphore Technologies SA).