Proteogenomic profiling predicts outcomes of adjuvant chemotherapy in extrahepatic cholangiocarcinoma.

Background & Aims: Cholangiocarcinoma is a heterogeneous disease, and its molecular characteristics and biomarkers and not yet fully understood. Here we performed comprehensive proteogenomic analyses to investigate the molecular landscape of extrahepatic cholangiocarcinoma (EH-CCA).

Methods: To identify potential biomarkers, prespecified exploratory analyses were conducted within the STAMP trial-a randomized phase 2 trial of adjuvant capecitabine or gemcitabine plus cisplatin (GemCis) for patients with resected EH-CCA.

Upregulation of interferon-γ response genes in monocytes and T cells identified by single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis.

Introduction: Our aim was to investigate the insufficiently understood differences in the immune system between anti-citrullinated peptide antibody (ACPA)-positive (ACPA) and ACPA-negative (ACPA) early rheumatoid arthritis (eRA) patients.

Methods: We performed multiple cytokine assays using sera from drug-naïve ACPA and ACPA eRA patients. Additionally, we conducted single-cell RNA sequencing of CD45 cells from peripheral blood samples to analyze and compare the distribution and functional characteristics of the cell subsets based on the ACPA status.

Development of Spondyloarthritis After COVID-19 in HLA-B27-Positive Monozygotic Twins: Case Reports With Single Cell Transcriptome Profiling.

A subset of spondyloarthritis (SpA) called 'reactive arthritis' is triggered by causal pathogens, usually bacteria related to venereal disease or gastrointestinal infection. During the outbreak of coronavirus disease 2019 (COVID-19), there have been case reports about SpA after COVID-19, but the causality is still elusive. We described cases of 23-year-old monozygotic twins both diagnosed with SpA after COVID-19.

Differential effects of periodontal microbiome on the rheumatoid factor induction during rheumatoid arthritis pathogenesis.

Association between exposure to periodontal bacteria and development of autoantibodies related to rheumatoid arthritis (RA) has been widely accepted; however, direct causal relationship between periodontal bacteria and rheumatoid factor (RF) is currently not fully understood. We investigated whether periodontal bacteria could affect RF status. Patients with preclinical, new-onset, or chronic RA underwent periodontal examination, and investigation of subgingival microbiome via 16S rRNA sequencing.

An efficient and tunable parameter to improve variant calling for whole genome and exome sequencing data.

Next generation sequencing (NGS) has traditionally been performed in various fields including agricultural to clinical and there are so many sequencing platforms available in order to obtain accurate and consistent results. However, these platforms showed amplification bias when facilitating variant calls in personal genomes. Here, we sequenced whole genomes and whole exomes from ten Korean individuals using Illumina and Ion Proton, respectively to find the vulnerability and accuracy of NGS platform in the GC rich/poor area.

Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas.

Despite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues.

Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer.

Background: Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown.

Objective: Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA.

Design, Settings, And Participants: We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization.

Genomic landscape of endometrial stromal sarcoma of uterus.

Although recurrent gene fusions such as JAZF1-JJAZ1 are considered driver events for endometrial stromal sarcoma (ESS) development, other genomic alterations remain largely unknown. In this study, we performed whole-exome sequencing, transcriptome sequencing and copy number profiling for five ESSs (three low-grade ESS (LG-ESS) and two undifferentiated uterine sarcomas (UUSs)). All three LG-ESSs exhibited either one of JAZF1-SUZ12, JAZF1-PHF1 and MEAF6-PHF1 fusions, whereas the two UUSs did not.

Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four-stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a 'parallel' evolution of synchronous adenoma-to-carcinoma, rather than a 'stepwise' evolution.

Subclonal Genomic Architectures of Primary and Metastatic Colorectal Cancer Based on Intratumoral Genetic Heterogeneity.

Purpose: The intratumoral heterogeneity (ITH) and the evolution of genomic architectures associated with the development of distant metastases are not well understood in colorectal cancers.

Experimental Design: We performed multiregion biopsies of primary and liver metastatic regions from five colorectal cancers with whole-exome sequencing and copy number profiling.

Results: In addition to a substantial level of genetic ITH, multiregion genetic profiling identifies the subclonal mutational architecture, leading to the region-based or spatial categorization of somatic mutations and the inference of intratumoral evolutionary history of cancers.

Genomic differences between pure ductal carcinoma in situ and synchronous ductal carcinoma in situ with invasive breast cancer.

Although ductal carcinoma in situ (DCIS) precedes invasive ductal carcinoma (IDC), the related genomic alterations remain unknown. To identify the genomic landscape of DCIS and better understand the mechanisms behind progression to IDC, we performed whole-exome sequencing and copy number profiling for six cases of pure DCIS and five pairs of synchronous DCIS and IDC. Pure DCIS harbored well-known mutations (e.

Progression of naive intraepithelial neoplasia genome to aggressive squamous cell carcinoma genome of uterine cervix.

Although cervical intraepithelial neoplasia (CIN) is considered a neoplasia, its genomic alterations remain unknown. For this, we performed whole-exome sequencing and copy number profiling of three CINs, a microinvasive carcinoma (MIC) and four cervical squamous cell carcinomas (CSCC). Both total mutation and driver mutation numbers of the CINs were significantly fewer than those of the MIC/CSCCs (P = 0.

MAP: Mutation Arranger for Defining Phenotype-Related Single-Nucleotide Variant.

Next-generation sequencing (NGS) is widely used to identify the causative mutations underlying diverse human diseases, including cancers, which can be useful for discovering the diagnostic and therapeutic targets. Currently, a number of single-nucleotide variant (SNV)-calling algorithms are available; however, there is no tool for visualizing the recurrent and phenotype-specific mutations for general researchers. In this study, in order to support defining the recurrent mutations or phenotype-specific mutations from NGS data of a group of cancers with diverse phenotypes, we aimed to develop a user-friendly tool, named mutation arranger for defining phenotype-related SNV (MAP).

The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers.

Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of EGC to AGC, it is required to disclose EGC and AGC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (five EGCs and four AGCs) and eight MS-stable (MSS) gastric cancers (four EGCs and four AGCs).

Regional biases in mutation screening due to intratumoural heterogeneity of prostate cancer.

Intratumoural heterogeneity (ITH) leads to regional biases of the mutational landscape in a single tumour and may influence the single biopsy-based clinical diagnosis and treatment decision. To evaluate the extent of ITH in unifocal prostate cancers (PCAs), we analysed multiple regional biopsies from three PCAs, using whole-exome sequencing, DNA copy number and gene expression profiling analyses. A substantial level of ITH was identified, in that 0-61% and 18-71% of somatic variants were common or private, respectively, within a given cancer.