Novel PTCH1 and concurrent TP53 mutations in four patients with numerous non-syndromic basal cell carcinomas: The paradigm of oncogenic synergy

There has been a significant increase in basal cell carcinoma (BCC) incidence, the most common cancer in humans and the age of presentation with the first diagnosis of BCC has decreased in past decades. In this study, we investigated the possibility of genetic markers that can lead to earlier and closer observation of patients at high risk for development of multiple BCCs. The overall goal is to decrease the morbidity and the economic burden of diagnosis and treatment of recurring and/or advanced BCCs. Four patients with numerous BCCs, some of them exceptionally large, were included in this study. A sample of representative BCCs, normal non–sun-exposed skin and blood samples were obtained from each patient. Whole-exome sequencing of DNA was conducted on all samples, and a series of bioinformatics filtering was performed to identify potentially pathogenic sequence variants. The analysis of the data resulted in detection of oncogenic mutations in PTCH1, two of which being novel, and concurrent mutations in TP53 in BCC tumours of all four patients. Such mutations may explain the numerous and postexcision recurring nature of the BCCs of exceptionally large size observed in all these patients, and they can be suggested to serve as a genetic marker for high-risk patients for early detection, prognostication and close follow-up

Colchicine and Cardiovascular Outcomes: A Critical Appraisal of Recent Studies

Purpose of review: Recent studies have demonstrated an important role for inflammation in the pathogenesis of atherosclerotic cardiovascular disease. Several studies have investigated the efficacy of colchicine (a widely used and safe anti-inflammatory drug) in patients with atherosclerosis. This review explains the rationale for the use of colchicine in this setting, and critically appraises recent outcomes trials. Recent findings: Two large randomised-controlled trials LoDoCo2 (included patients with chronic coronary syndromes) and COLCOT (acute coronary syndromes) have demonstrated reductions in atherosclerotic cardiovascular events, but not mortality. A smaller study (COPS) found no beneficial effect of colchicine but was probably underpowered. Summary: Colchicine is effective at reducing cardiovascular events in chronic and acute coronary syndromes, although reductions in all-cause mortality have not been demonstrated during the period of follow up in trials to date. Mild gastrointestinal symptoms are the most commonly reported adverse effects, although in well-designed randomised controlled trials these are relatively uncommon