Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.

Rechallenge of immune checkpoint inhibitors in a case with adverse events inducing myasthenia gravis.

The mechanism(s) of immune checkpoint inhibitor (ICI)-induced myasthenia gravis (MG), an immune-related adverse event (irAE) that is fatal and limits subsequent ICI use, remain unexplored. Here, through comparative genomic analysis, we identified a pathogenic p.S467C germline variant in in a thymoma case with ICI-induced MG, which was found to be associated with fatty acid oxidation through its regulation on L-carnitine levels.

Tumor mutational burden and efficacy of chemotherapy in lung cancer.

Purpose: TMB is one of the potent biomarkers of response to immune checkpoint blockade. The association between TMB and efficacy of chemotherapy in advanced lung cancer has not been comprehensively explored.

Methods: Ninety lung cancer patients receiving first-line chemotherapy with large panel next-generation sequencing data of pre-treatment tumor tissue were identified.

Unique genomic alterations of cerebrospinal fluid cell-free DNA are critical for targeted therapy of non-small cell lung cancer with leptomeningeal metastasis.

We reported unique molecular features of cerebrospinal fluid (CSF) of NSCLC patients with leptomeningeal metastasis (LM), suggesting to establish CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma and CSF from 131 NSCLC patients with LM, and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors.

Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis.

We reported unique molecular features of cerebrospinal fluid (CSF) of nonsmall cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM), suggesting establishing CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma, and CSF from 131 NSCLC patients with LM and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors.

Abnormal B-cell development in TIMP-deficient bone marrow.

Bone marrow (BM) is the primary site of hematopoiesis and is responsible for a lifelong supply of all blood cell lineages. The process of hematopoiesis follows key intrinsic programs that also integrate instructive signals from the BM niche. First identified as an erythropoietin-potentiating factor, the tissue inhibitor of metalloproteinase (TIMP) protein family has expanded to 4 members and has widely come to be viewed as a classical regulator of tissue homeostasis.

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of External Ventricular and Lumbar Drainage-Associated Ventriculitis and Meningitis.

Metagenomic next-generation sequencing (mNGS) has become a widely used technology that can accurately detect individual pathogens. This prospective study was performed between February 2019 and September 2019 in one of the largest clinical neurosurgery centers in China. The study aimed to evaluate the performance of mNGS on cerebrospinal fluid (CSF) from neurosurgical patients for the diagnosis of external ventricular and lumbar drainage (EVD/LD)-associated ventriculitis and meningitis (VM).

Genetic aberrations in Chinese pancreatic cancer patients and their association with anatomic location and disease outcomes.

Objectives: Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancer patients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options.

Method: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens of 90 pancreatic cancer patients and sequenced.

Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study.

The gut microbiota is closely associated with colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating bacterial DNA in colorectal neoplasia patients remained unexplored. This proof-of-concept study aims to characterize alterations of circulating bacterial DNA in colorectal neoplasia patients.

Durable Complete Response to Alectinib in a Lung Adenocarcinoma Patient With Brain Metastases and Low-Abundance Variant in Liquid Biopsy: A Case Report.

fusions are targetable oncogenic drivers in a subset of advanced non-small cell lung cancer (NSCLC) patients that can benefit from selected ALK inhibitors. Precise detection of fusions may yield critical information for selection of appropriate therapy and hence improve patient survival. Analysis of circulating tumor DNA (ctDNA) in liquid biopsies using next generation sequencing (NGS) prior to or during treatment hold great promise for disease monitoring and treatment guidance of various cancers including NSCLC.

EML4-ALK, a potential therapeutic target that responds to alectinib in ovarian cancer.

Ovarian cancer is prone to recurrence and chemotherapy resistance. Ovarian tumours of some patients have been positive for anaplastic lymphoma kinase fusion gene expression (ALK+). Preclinical studies indicate that anaplastic lymphoma kinase inhibitor can suppress the growth of ovarian cancer cells and transplantation tumours.

Primary pulmonary lymphoepithelioma-like carcinoma is characterized by high PD-L1 expression, but low tumor mutation burden.

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer (NSCLC). There are few reported studies on the relationship between programmed death ligand-1 (PD-L1) expression and genomics features of this distinct NSCLC subtype. Our study aimed to investigate the expression levels of PD-L1 to determine their clinical value and to identify genetic alterations in PLELC.

Quantitative characterization of tumor cell-free DNA shortening.

Background: Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application.

Results: Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166 bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150 bp).

Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients.

Objectives: The application of circulating tumor DNA (ctDNA) monitoring after resection in pathologic(p) stage I lung adenocarcinoma (LUAD) patients remains controversial and it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. We aim to assess the utility of ctDNA in tracking early recurrence or metastasis following surgery and reveal the genetic differences between GGO and non-GGO.

Materials And Methods: Tumor tissues and matched postoperative plasma samples were collected from a total of 82 (p)stage I LUAD patients.

Clinical and molecular characteristics of Chinese non-small cell lung cancer patients with ERBB2 transmembrane domain mutations.

Transmembrane domain (TMD) mutations of ERBB2 have previously been reported in lung cancer patients in addition to well-studied kinase domain (KD) mutations, which may stabilize ERBB2 heterodimerization with other EGFR family members and favor a kinase active conformation. However, the frequency and clinical significance of ERBB2 TMD mutations in Chinese population is unknown. We prospectively analyzed the next-generation sequencing data of 34 368 Chinese lung cancer patients with different sample types, including tumor tissue, plasma, cerebrospinal fluid, and pleural effusion.

Variability of EGFR exon 20 insertions in 24 468 Chinese lung cancer patients and their divergent responses to EGFR inhibitors.

EGFR exon 20 insertions (EGFR e20ins) account for up to 10% of EGFR mutations in lung cancer; however, tumors with EGFR e20ins had poor response rates to EGFR tyrosine kinase inhibitors (TKIs) including gefitinib, erlotinib, afatinib, and osimertinib, and the heterogeneity of EGFR e20ins further complicates the clinical studies. Here, we retrospectively screened next-generation sequencing (NGS) data from 24 468 lung cancer patients, and a total of 85 unique EGFR e20ins variants were identified in 547 cases (2.24%), with p.

Identifying novel oncogenic mutations and characterising their sensitivity to RET-specific inhibitors.

Background: Rearranged during transfection () is a well-known proto-oncogene. Multiple oncogenic alterations have been identified, including fusions and mutations. Although fusions have been reported in multiple cancers, mutations were mainly found in multiple endocrine neoplasia type 2 and medullary thyroid carcinoma.

Wait-and-See Treatment Strategy Could be Considered for Lung Adenocarcinoma with Special Pleural Dissemination Lesions, and Low Genomic Instability Correlates with Better Survival.

Background: This study aimed to evaluate the feasibility of a wait-and-see strategy for non-small cell lung cancer (NSCLC) patients with special pleural dissemination lesions (r-pM1a and s-pM1a). Furthermore, the study characterized genomic alternations about disease progression.

Methods: For this study, 131 NSCLC patients with a diagnosis of pM1a were retrospectively selected.

Acquired multiple secondary mutations upon PARPi resistance in a metastatic pancreatic cancer patient harboring a germline mutation.

PARP inhibitor (PARPi) therapies have been approved for treating multiple germline mutated (gm) advanced cancers including metastatic pancreatic cancer. Although significantly prolonged progression-free survival was observed in gm pancreatic cancer patients, there was no improved overall survival. The underlined resistant mechanism to PARPi therapy is worth pursuing.

Author Correction: Human somatic cell mutagenesis creates genetically tractable sarcomas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in wild-type advanced non-small cell lung cancer.

Background: Immunotherapy has become an important treatment option for patients with advanced non-small cell lung cancer (NSCLC). At present, none of these existing biomarkers can effectively stratify true responders and there is an urgent need for identifying novel biomarkers. Exosomes derived from the serum of patients with cancer have been proven to be reliable markers for cancer diagnosis.

Genomic dissection of gastrointestinal and lung neuroendocrine neoplasm.

Objective: Neuroendocrine neoplasms (NENs) are relatively rare and heterogeneous malignancies with two major subtypes: low-grade neuroendocrine tumor (NET) and high-grade neuroendocrine carcinoma (NEC). Comprehensive molecular characterization of NENs is needed to refine our understanding of the biological underpinnings of different NEN subtypes and to predict disease progression more accurately.

Methods: We performed whole-exome sequencing (WES) of NEN samples from 49 patients (25 NETs and 24 NECs) arising from the stomach, intestines or lung.