Open-Source Bioinformatic Pipeline to Improve PMS2 Genetic Testing Using Short-Read NGS Data.

The molecular diagnosis of mismatch repair-deficient cancer syndromes is hampered by difficulties in sequencing the PMS2 gene, mainly owing to the PMS2CL pseudogene. Next-generation sequencing short reads cannot be mapped unambiguously by standard pipelines, compromising variant calling accuracy. This study aimed to provide a refined bioinformatic pipeline for PMS2 mutational analysis and explore PMS2 germline pathogenic variant prevalence in an unselected hereditary cancer (HC) cohort.

Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation.

Background: Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial.

Role of psychological background in cancer susceptibility genetic testing distress: It is not only about a positive result.

Clinical and familial factors predict psychological distress after genetic testing for cancer susceptibility. However, the contribution of an individual's psychological background to such distress is unclear. This study aims to analyze the psychological impact of genetic testing and to identify the profile of individuals at higher risk.

Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships.

Background: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors.

Paired Somatic-Germline Testing of 15 Polyposis and Colorectal Cancer-Predisposing Genes Highlights the Role of APC Mosaicism in de Novo Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome responsible for 1% of colorectal cancers (CRCs). Up to 90% of classic FAPs are caused by inactivating mutations in APC, and mosaicism has been previously reported in 20% of de novo cases, usually linked to milder phenotypic manifestations. This study aimed to explore the prevalence of mosaicism in 11 unsolved cases of classic FAP and to evaluate the diagnostic yield of somatic testing.

Diagnosis and management of an endometrial cancer patient with Cowden syndrome.

Somatic PTEN alterations are common in endometrial carcinoma (EC), but in rare cases PTEN mutations are associated with inherited syndromes. Here, we present a case of Cowden syndrome-associated EC. We discuss clinical, pathologic and molecular features of her tumor and PTEN-mutated EC, inherited syndromes predisposing to EC and PTEN-targeted therapies.

Patients' and professionals' perspective of non-in-person visits in hereditary cancer: predictors and impact of the COVID-19 pandemic.

Purpose: To identify predictors of patient acceptance of non-in-person cancer genetic visits before and after the COVID-19 pandemic and assess the preferences of health-care professionals.

Methods: Prospective multicenter cohort study (N = 578, 1 February 2018-20 April 2019) and recontacted during the COVID-19 lockdown in April 2020. Health-care professionals participated in May 2020.

Comprehensive Constitutional Genetic and Epigenetic Characterization of Lynch-Like Individuals.

The causal mechanism for cancer predisposition in Lynch-like syndrome (LLS) remains unknown. Our aim was to elucidate the constitutional basis of mismatch repair (MMR) deficiency in LLS patients throughout a comprehensive (epi)genetic analysis. One hundred and fifteen LLS patients harboring MMR-deficient tumors and no germline MMR mutations were included.

Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.

Purpose: Few and small studies have been reported about multigene testing usage by massively parallel sequencing in European cancer families. There is an open debate about what genes should be tested, and the actionability of some included genes is under research.

Methods: We investigated a panel of 34 known high/moderate-risk cancer genes, including 16 related to breast or ovarian cancer (BC/OC) genes, and 63 candidate genes to BC/OC in 192 clinically suspicious of hereditary breast/ovarian cancer (HBOC) Spanish families without pathogenic variants in BRCA1 or BRCA2 (BRCA1/2).

[Study of lipids (cholesterol, triglycerides and phospholipids), plasma lipoproteins (HDL-cholesterol) and apoproteins (apo A and apo B in patients with acute myocardial infarction].

Several lipid parameters were evaluated in 88 patients with acute myocardial infarction (AMI). A reduction in cholesterol and phospholipid level was observed, with minimal values between the days 10-20, followed by a subsequent increase. Triglycerides increased after 12-14 hours, with a maximal value after 20-30 days.

Action of persistent administration of a hapten with a reactive group (TNBS) and mono-or divalent conjugates of hapten to molecules without other reactive groups on anti-TNP-LPS response.

The intrinsic tolerization mechanisms of the B cell have been postulated either at the level of membrane receptor blockade, before the appearance of membrane receptors, or more intracellularly. For the first possibility a certain multivalence or epitope/hapten density of the antigen molecule is required. Tolerance has been induced by free haptens that possess a reactive group, but haptens lacking such a reactive group may not necessarily be tolerized.

[Parallelism between the kinetics of cross-reaction responses (anti-TNP and anti-DNP) and differences from the anti-LPS response when challenged with TNP-LPS immunization].

The multi-functionality of a given antibody, even monoclonal antibody has recently been shown; this raises the possibility that the specificity of an antiserum be due to a population phenomena; i.e., the specificity would be the net result of the affinity of the various antibodies to the same hapten or antigenic determinant.

Stimulation of IgG antibody formation by sublethal irradiation during persistently repeated immunization with Brucella abortas.

Whole-body irradiation with 600 rads 8 or 10 days after the beginning of persistently repeated Brucella abortus immunization in the rabbit produces little change in the response. By contrast, irradiation with the same dose 2, 4 or 6 days after the beginning of repeated immunization stimulates the IgG response. This effect is explained by a repopulation of antigen-sensitive cells from precursor cells to a higher level than that previous to irradiation.

Acute renal insufficiency in the rabbit by glycerol.

The appearance of an acute renal insufficiency in the rabbit, after glycerol injection (10, 13 or 15 ml/kg of a 50% solution) is investigated. After a 24 hours of intoxication, especially in the ten following days, cylinders, erythrocytes and renal cells appear in the urine sediment. Proteinuria appears after 24 hours and practically disappears after 72 h.