Acetaldehyde and defective mismatch repair increase colonic tumours in a Lynch syndrome model with Aldh1b1 inactivation.

ALDH1B1 expressed in the intestinal epithelium metabolises acetaldehyde to acetate, protecting against acetaldehyde-induced DNA damage. MSH2 is a key component of the DNA mismatch repair (MMR) pathway involved in Lynch syndrome (LS)-associated colorectal cancers. Here, we show that defective MMR (dMMR) interacts with acetaldehyde, in a gene/environment interaction, enhancing dMMR-driven colonic tumour formation in a LS murine model of Msh2 conditional inactivation (Lgr5-CreER; Msh2flox/-, or Msh2-LS) combined with Aldh1b1 inactivation.

Ethanol-induced formation of colorectal tumours and precursors in a mouse model of Lynch syndrome.

Lynch syndrome (LS) confers inherited cancer predisposition due to germline mutations in a DNA mismatch repair (MMR) gene, e.g. MSH2.

Molecular pathology of Lynch syndrome.

Lynch syndrome (LS) is characterised by predisposition to colorectal, endometrial, and other cancers and is caused by inherited pathogenic variants affecting the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. It is probably the most common predisposition to cancer, having an estimated prevalence of between 1/100 and 1/180. Resources such as the International Society for Gastrointestinal Hereditary Cancer's MMR gene variant database, the Prospective Lynch Syndrome Database (PLSD), and the Colon Cancer Family Register (CCFR), as well as pathological and immunological studies, are enabling advances in the understanding of LS.

ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma.

Spiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation and potential for malignant transformation and aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma-spiradenoma hybrid tumors, and 24 low- and high-grade spiradenocarcinoma cases, together with morphologically benign precursor regions of these cancers. We reveal somatic or germline alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas.

Interferon-free therapy in hepatitis C virus mixed cryoglobulinaemia: a prospective, controlled, clinical and quality of life analysis.

Background: Cryoglobulinaemic vasculitis (CV) is a lymphoproliferative disorder related to hepatitis C virus (HCV) infection; anti-viral therapy is the first therapeutic option. CV can be incapacitating, compromising the patients' quality of life (QoL). In a controlled study, interferon-based therapy was associated with a lower virological response in vasculitic patients than in patients without vasculitis.