Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression.

Background: Gastric intestinal metaplasia (IM) is a precancerous stage spanning a morphological spectrum that is poorly represented by human cell line models.

Objective: We aim to establish and characterise human IM cell models to better understand IM progression along the cancer spectrum.

Design: A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established.

Mutational landscape of normal epithelial cells in Lynch Syndrome patients.

Lynch Syndrome (LS) is an autosomal dominant disease conferring a high risk of colorectal cancer due to germline heterozygous mutations in a DNA mismatch repair (MMR) gene. Although cancers in LS patients show elevated somatic mutation burdens, information on mutation rates in normal tissues and understanding of the trajectory from normal to cancer cell is limited. Here we whole genome sequence 152 crypts from normal and neoplastic epithelial tissues from 10 LS patients.

Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles.

Objective: Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs.

Design: We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC.

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.

Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis.

RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation.

Objective: Serrated polyps (hyperplastic polyps, sessile or traditional serrated adenomas), which can arise in a sporadic or polyposis setting, predispose to colorectal cancer (CRC), especially those with microsatellite instability (MSI) due to MLH1 promoter methylation (MLH1). We investigate genetic alterations in the serrated polyposis pathway.

Design: We used a combination of exome sequencing and target gene Sanger sequencing to study serrated polyposis families, sporadic serrated polyps and CRCs, with validation by analysis of The Cancer Genome Atlas (TCGA) cohort, followed by organoid-based functional studies.

Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer.

Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and epigenetic perturbations and unique mutational signatures.

Accuracy of intraoperative frozen section analysis of nasopharyngeal carcinoma resection margins.

Background: Frozen section analysis (FSA) is frequently used in salvage surgery for recurrent or residual nasopharyngeal carcinoma (rNPC) after radiotherapy to ensure adequate tumor removal. However, the diagnostic accuracy of FSA in rNPC has never been clearly established. We believe that this is the first study to specifically address these issues.

Duodenal GIST metastasized to skull and orbit managed by surgery: a case report.

We report a 26-year-old man with 6 years, history of duodenal gastrointestinal stromal tumor (GIST) with liver, peritoneum and lung metastases. He presented with left eye ptosis, diplopia, left facial numbness and a left temporal fossa mass that was confirmed to be GIST with left skull and left orbit metastases. Craniectomy with cranioplasty, tumor excision and decompression were performed.

Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer.

Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated.