Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path_APC) and pathogenic mismatch repair gene (path_MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path_APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years.
View Article and Find Full Text PDFBackground: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas.
View Article and Find Full Text PDFBackground: Morning reports are an essential component of physicians' daily work. Attending morning reports is prioritized by junior doctors as it provides them with an opportunity to learn diagnostic reasoning through discussion of cases. While teaching formats during morning reports have previously been reported, an in-depth analysis of what learning opportunities exist, e.
View Article and Find Full Text PDFGenetic conditions are often familial, but not all relatives receive counseling from the same institution. It is therefore necessary to ensure consistency in variant interpretation, counseling practices, and clinical follow up across health care providers. Furthermore, as new possibilities for gene-specific treatments emerge and whole genome sequencing becomes more widely available, efficient data handling and knowledge sharing between clinical laboratory geneticists and medical specialists in clinical genetics are increasingly important.
View Article and Find Full Text PDFUgeskr Laeger
September 2023
Polygenic risk scores (PRS) identify at-risk individuals for many common diseases. A discussion of strengths and limitations is carried out in this review. PRS complement traditional genetic testing and have shown utility in establishing a proper diagnosis and guiding primary and secondary prevention.
View Article and Find Full Text PDFHydatidiform moles are rare and thus most pathologists and geneticists have little experience with their diagnosis. It is important to promptly and correctly identify hydatidiform moles given that they are premalignant disorders associated with a risk of persistent gestational trophoblastic disease and gestational trophoblastic neoplasia. Improvement in diagnosis can be achieved with uniformization of diagnostic criteria and establishment of algorithms.
View Article and Find Full Text PDFHydatidiform moles (HMs) are divided into two types: partial hydatidiform mole (PHM) which is most often diandric monogynic triploid and complete hydatidiform mole (CHM) which is most often diploid androgenetic. Morphological features and p57 immunostaining are routinely used to distinguish both entities. Genetic analyses are required in challenging cases to determine the parental origin of the genome and ploidy.
View Article and Find Full Text PDFJuvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected in SMAD4 or BMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant in BMPR1A or SMAD4.
View Article and Find Full Text PDFBackground: Gestational trophoblastic disease comprises hydatidiform moles and a rare group of malignancies that derive from trophoblasts. Although there are typical morphological features that may distinguish hydatidiform moles from non-molar products of conception, such features are not always present, especially at early stages of pregnancy. Furthermore, mosaic/chimeric pregnancies and twin pregnancies make pathological diagnosis challenging while trophoblastic tumours can also pose diagnostic problems in terms of their gestational or non-gestational origin.
View Article and Find Full Text PDFPhenomenon: The morning report is one of the longest surviving hospital practices. Most studies of the morning report focus on the effectiveness of formal medical training, while focus on social and communicative aspects is rarer. This study explores the social interactions and communication in morning reports, examining the ways in which they contribute to the construction of professional identity and socialization into the community of the clinical department.
View Article and Find Full Text PDFPeutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%-15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival.
View Article and Find Full Text PDFAim: Our goal was to describe a precision medicine program in a regional academic hospital, characterize features of included patients and present early data on clinical impact.
Materials And Methods: We prospectively included 163 eligible patients with late-stage cancer of any diagnosis from June 2020 to May 2022 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference.
Introduction: Identifying hydatidiform moles (HMs) is crucial due to the risk of gestational trophoblastic neoplasia. When a HM is suspected on clinical findings, surgical termination is recommended. However, in a substantial fraction of the cases, the conceptus is actually a non-molar miscarriage.
View Article and Find Full Text PDFIn most patients with juvenile polyposis Syndrome, it is possible to detect a pathogenic germline variant in or . It is well known that patients with a pathogenic variant in have a higher risk of gastric polyposis and gastric cancer compared to carriers, but the natural history of gastric involvement is poorly described. We aimed to systematically review endoscopic and histopathological gastric findings in Danish patients with pathogenic variants in This was a retrospective, cross-sectional study including endoscopic and histological gastric findings in all known Danish patients with pathogenic variants in .
View Article and Find Full Text PDFBackground: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of cysts and a decline of renal function. The clinical feasibility of the number of potential disease-modifying drugs is limited by systemic adverse effects. We hypothesize that megalin, a multiligand endocytic receptor expressed in the proximal tubule, may be used to facilitate drug uptake into cysts, thereby allowing for greater efficacy and fewer side effects.
View Article and Find Full Text PDFWe present a three-generation family with an AXIN2 variant and a family history of colorectal cancer (CRC), colon polyps and tooth agenesis. A likely pathogenic variant was detected in the AXIN2 gene (c.1994dup; p.
View Article and Find Full Text PDFHereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes..
View Article and Find Full Text PDFHereditary polyposis syndromes (HPS) are a group of rare, inherited syndromes characterised by the presence of histopathological specific or numerous intestinal polyps and a high risk of intestinal and extraintestinal cancer. During the last decade, several new HPS have been discovered, as it is possible to detect pathogenic germline variants in genes not previously known to be associated with polyposis. This review summarises the current knowledge on the syndromes and discusses genetic testing as part of the diagnostic pipeline when suspecting a polyposis syndrome.
View Article and Find Full Text PDFBackground: Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance.
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