Ming Tsao

IntroductionMorphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment.MethodsWES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of the study cases was characterized by the HTG EdgeSeq Precision Immuno-Oncology Panel.ResultsBy WES data, 11 cases were classified as SPLC and seven cases as IPM. Two cases …

In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional minor corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper.

The Canadian NTRK (CANTRK) study is an interlaboratory comparison ring study to optimize testing for neurotrophic receptor tyrosine kinase (NTRK) fusions in Canadian laboratories. Sixteen diagnostic laboratories used next-generation sequencing (NGS) for NTRK1, NTRK2, or NTRK3 fusions. Each laboratory received 12 formalin-fixed, paraffin-embedded tumor samples with unique NTRK fusions and two control non-NTRK fusion samples (one ALK and one ROS1). Laboratories used validated protocols for NGS fusion detection. Panels included Oncomine Comprehensive Assay v3, Oncomine Focus Assay, Oncomine Precision Assay, AmpliSeq for Illumina Focus, TruSight RNA Pan-Cancer Panel, FusionPlex Lung, and QIAseq Multimodal Lung. One sample was withdrawn from analysis because of sample quality issues. Of the remaining 13 samples, 6 of 11 NTRK fusions and both control fusions were detected …

We employ wide‐field second harmonic generation (SHG) microscopy together with nonlinear Stokes polarimetry for quick ultrastructural investigation of large sample areas (700 μm × 700 μm) in thin histology sections. The Stokes vector components for SHG are obtained from the polarimetric measurements with incident and outgoing linear and circular polarization states. The Stokes components are used to construct the images of polarimetric parameters and deduce the maps of ultrastructural parameters of achiral and chiral nonlinear susceptibility tensor components ratios and cylindrical axis orientation in fibrillar materials. The large area imaging was employed for lung tumor margin investigations. The imaging shows reduced SHG intensity, increased achiral susceptibility ratio values, and preferential orientation of collagen strands along the boarder of tumor margin. The wide‐field Stokes polarimetric SHG …

Methods: Patients with clinical T< 4cm N0 NSCLC planned for surgical resection at Princess Margaret/University Health Network underwent plasma ctDNA assessment before and after surgery (∼ 1 month and 1 year). Minimal residual disease (MRD) was detected using the highly sensitive and specific tumor-informed RaDaR® assay (NeoGenomics, Durham, NC), testing up to 48 tumor-specific variants in plasma with a limit of detection 95 of 0.0011% variant allele fraction.Results: From Aug 2021-Feb 2023, 129 patients were enrolled and 70 had sufficient tissue for ctDNA bespoke panel generation (Table 1). Preoperative ctDNA was detected in 17/69 (24.6%) patients (with a lower detection rate of 9/50 or 18% in pathologic stage I NSCLC). All but one patient (1/17; 94.1%) had ctDNA clearance with surgery at 1-month landmark timepoint. This patient with occult N2 disease remains disease-free radiographically on …

The high expression of epidermal growth factor receptor (EGFR) in carcinomas from multiple tissue sites led to preclinical studies and early trials assessing the efficacy of EGFR inhibitors in multiple cancer types. In these early studies, one class of EGFR inhibitors that targets the tyrosine kinase domain of the receptor proved effective in some patients with lung adenocarcinoma. It was later shown that mutations in the tyrosine kinase (TK) domain rather than the EGFR expression predicted response to this class of drugs. First-, second-, and third-generation EGFR TKIs (tyrosine kinase inhibitors) were successively developed and became the standard of care in the treatment of patients with EGFR-mutated lung cancer. Despite the improvements in survival achieved by these drugs, patients still face challenges as mechanisms of resistance eventually develop and lead to disease progression. This chapter will outline …

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths worldwide. The centrosome is the main microtubule-organizing center in animal cells and centrosome amplification is a hallmark of cancer cells. To investigate the importance of centrosomes in colorectal cancer, we induced centrosome loss in normal and cancer human-derived colorectal organoids using centrinone B, a Polo-like kinase 4 (Plk4) inhibitor. We show that centrosome loss represses human normal colorectal organoid growth in a p53-dependent manner in accordance with previous studies in cell models . However, cancer colorectal organoid lines exhibited different sensitivities to centrosome loss independently of p53. Centrinone-induced cancer organoid growth defect/death positively correlated with a loss of function mutation in the APC gene, suggesting a causal role of the hyperactive WNT pathway. Consistent with this notion, β-catenin inhibition using XAV-939 or ICG-001 partially prevented centrinone-induced death and rescued the growth of APC-mutant organoid lines. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in APC-mutant colorectal cancer independently of the classical p53 pathway.

Introduction: Patients with early-stage lung cancers have a high risk of relapse and death even after curative surgery. Detection of circulating tumour DNA (ctDNA) in plasma perioperatively is associated with shorter recurrence free survival (RFS). ctDNA-Lung-Detect is an investigator-initiated prospective study of ctDNA detection and association with RFS in patients with early stage non-small cell lung cancer (NSCLC). Methods: Patients with clinically staged T<4cm N0 NSCLC planned for surgical resection at the Princess Margaret/University Health Network underwent ctDNA assessment before and after surgery (~1 month and 1 year). ctDNA minimal residual disease (MRD) was detected using the highly sensitive and specific tumor-informed Residual Disease and Recurrence (RaDaR®, Inivata, Cambridge, UK) assay, which can track up to 48 tumor-specific variants in plasma. Results: Since August 2021, 64 …