Universal molecular screening does not effectively detect Lynch syndrome in clinical practice.

Background: Lynch syndrome (LS) due to an inherited damaging mutation in mismatch repair (MMR) genes comprises 3% of all incident colorectal cancer (CRC). Molecular testing using immunohistochemistry (IHC) for MMR proteins is a recommended screening tool to identify LS in incident CRC. This study assessed outcomes of population-based routine molecular screening for diagnosis of LS in a regional center.

A deleterious RNF43 germline mutation in a severely affected serrated polyposis kindred.

We report a germline nonsense mutation within the extracellular domain of the RING finger ubiquitin ligase RNF43, segregating with a severe form of serrated polyposis within a kindred. The finding provides evidence that inherited RNF43 mutations define a familial cancer syndrome.

Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.

Background: MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.

Trefoil factors: initiators of mucosal healing.

Maintaining the integrity of the gastrointestinal tract, despite the continual presence of microbial flora and injurious agents, is essential. Epithelial continuity depends on a family of small, yet abundant, secreted proteins--the trefoil factors (TFFs). TFFs protect mucous epithelia from a range of insults and contribute to mucosal repair, although the signalling events that mediate these responses are only partially understood.

Distinctive patterns of gene expression in premalignant gastric mucosa and gastric cancer.

Current epidemiological evidence supports a pathogenetic model of gastric cancer involving intermediate stages that include chronic gastritis and intestinal metaplasia. This study explores the molecular features of gastric cancer and premalignant stages using DNA microarray-based gene expression profiling and relates these findings to clinical, pathological, and ethnic parameters. A total of 124 tumor and adjacent mucosa samples were analyzed using spotted cDNA microarrays containing 9381 nonredundant gene elements.

Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis-acting element.

Trefoil factor 2 (TFF2)/spasmolytic polypeptide (SP) is a highly stable peptide which is abundantly expressed and secreted by mucous cells of the stomach and which functions in gastric cytoprotection. Previous studies from our group have shown that TFF2 is an immediate early gene capable of regulating its own expression through activation of the TFF2 promoter. We therefore aimed to investigate the cis-acting elements mediating this response in AGS cells transfected with TFF2 promoter-reporter gene constructs, using a TFF2-expression system resembling physiologic paracrine conditions.

TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury.

Trefoil factor family 2 (TFF2), also known as spasmolytic polypeptide, is a member of the trefoil family of peptides and is expressed primarily in the mucous neck cells of the gastric mucosa. To study the physiologic role of TFF2, we have generated TFF2-deficient mice through targeted gene disruption. Homozygous mutant mice were viable and fertile without obvious gastrointestinal abnormalities.