In a fraction of families fulfilling the Amsterdam criteria for hereditary non-polyposis colorectal cancer, colorectal cancers are microsatellite stable and DNA mismatch repair gene (MMR) mutations are not found. These families were designated as familial colorectal cancer type X (FCCTX). We aimed to characterise a group of FCCTX families defined by the Amsterdam criteria and MSS tumours at clinical and molecular level. Twenty-four tumours from 15 FCCTX families were analysed for loss of known tumour suppressor gene (TSG) loci (APC, TP53, SMAD4 and DCC), MGMT and MMR genes promoter methylation, and also APC and KRAS somatic mutations. FCCTX families presented specific clinical features: absence of endometrial tumours, high adenoma/carcinoma ratio (1.91) and prevalence of rectal cancers (13/27, 48%). New molecular features were found: the majority of FCCTX tumours (13/18; 72%) presented TSG loss. TSG loss positive tumours presented frequent APC and KRAS somatic mutations and MGMT methylation [10/13 (77%), 7/13 (54%) and 6/11 (54%), respectively]. In TSG loss negative tumours (5/18; 28%), the same molecular events were found in 2/5 (40%), 2/5 (40%) and 1/3 (33%) tumours, respectively. Transition mutations in KRAS were more frequent among MGMT methylated tumours than in unmethylated [5/8 (63%) vs. 1/10 (10%), P = 0.03]. Although sharing similar clinical features, at least two different molecular entities should exist among FCCTX families, one whose tumours present frequent TSG loss, APC and KRAS somatic mutations, and MGMT promoter methylation, and a second, lesser predominant, with no evidence of TSG loss and rarely presenting promoter methylation.
Preservation of the alveolar bone is a determinant in the outcome of orthodontic treatment. Alveolar bone defects or a decrease of their height and width may occur due to common reasons such as inflammation, tooth extraction, or cleft lip and palate. The aim of this systematic review was to investigate and appraise the quality of the most up to date available evidence regarding the applications and effects of platelet-rich fibrin (PRF) in orthodontics. This study was carried out according to preferred reporting items for systematic reviews and meta-analyses guidelines using the following databases: Medline via PubMed, Cochrane Library, Web of Science Core Collection and EMBASE. The qualitative assessment of the included studies was performed using Cochrane Risk of Bias tool and ROBINS-I guidelines. Results: From a total of 489 studies, nine studies were selected. The majority of the included studies demonstrate that autogenous anterior iliac graft with PRF had a higher amount of newly formed bone. Furthermore, this review also suggests that the application of platelet derivatives in the extraction socket can accelerate orthodontic tooth movement. Despite the limitations in the included studies, this systematic review suggested that PRF can improve alveolar cleft reconstruction and orthodontic tooth movement.
Adenomas diagnosed before aged 40 years presented microsatellite instability only in patients from families with clinical criteria for Lynch syndrome. According to our results, to detect new cases of Lynch syndrome, family history is more important than microsatellite instability testing in adenomas from young patients.
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