227 results on '"Bronner M."'
Search Results
52. Hepatitis G virus co-infection does not alter the course of recurrent hepatitis C virus infection in liver transplantation recipients
- Author
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Cotler, S J, primary, Gretch, D R, additional, Bronner, M P, additional, Tateyama, H, additional, Emond, M J, additional, dela Rosa, C, additional, Perkins, J D, additional, and Carithers, R L, additional
- Published
- 1997
- Full Text
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53. Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport.
- Author
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Wittmaack, F M, primary, Gåfvels, M E, additional, Bronner, M, additional, Matsuo, H, additional, McCrae, K R, additional, Tomaszewski, J E, additional, Robinson, S L, additional, Strickland, D K, additional, and Strauss, J F, additional
- Published
- 1995
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54. Rare germline large rearrangements in the BRCA1/ 2 genes and eight candidate genes in 472 patients with breast cancer predisposition.
- Author
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Rouleau, E., Jesson, B., Briaux, A., Nogues, C., Chabaud, V., Demange, L., Sokolowska, J., Coulet, F., Barouk-Simonet, E., Bignon, Y., Bonnet, F., Bourdon, V., Bronner, M., Caputo, S., Castera, L., Delnatte, C., Delvincourt, C., Fournier, J., Hardouin, A., and Muller, D.
- Abstract
Hereditary breast cancers account for up to 5-10 % of breast cancers and a majority are related to the BRCA1 and BRCA2 genes. However, many families with breast cancer predisposition do not carry any known mutations for BRCA1 and BRCA2 genes. We explored the incidence of rare large rearrangements in the coding, noncoding and flanking regions of BRCA1/ 2 and in eight other candidate genes- CHEK2, BARD1, ATM, RAD50, RAD51, BRIP1, RAP80 and PALB2. A dedicated zoom-in CGH-array was applied to screen for rearrangements in 472 unrelated French individuals from breast-ovarian cancer families that were being followed in eight French oncogenetic laboratories. No new rearrangement was found neither in the genomic regions of BRCA1/ 2 nor in candidate genes, except for the CHEK2 and BARD1 genes. Three heterozygous deletions were detected in the 5′ and 3′ flanking regions of BRCA1. One large deletion introducing a frameshift was identified in the CHEK2 gene in two families and one heterozygous deletion was detected within an intron of BARD1. The study demonstrates the usefulness of CGH-array in routine genetic analysis and, aside from the CHEK2 rearrangements, indicates there is a very low incidence of large rearrangements in BRCA1/ 2 and in the other eight candidate genes in families already explored for BRCA1/ 2 mutations. Finally, next-generation sequencing should bring new information about point mutations in intronic and flanking regions and also medium size rearrangements. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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55. Non-Hodgkin lymphoma of the small intestine.
- Author
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Rubesin, S E, primary, Gilchrist, A M, additional, Bronner, M, additional, Saul, S H, additional, Herlinger, H, additional, Grumbach, K, additional, Levine, M S, additional, and Laufer, I, additional
- Published
- 1990
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56. Atypical hyperplastic polyps at double-contrast barium enema examination.
- Author
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Levine, M S, primary, Barnes, M J, additional, Bronner, M P, additional, Rubesin, S E, additional, and Saul, S H, additional
- Published
- 1990
- Full Text
- View/download PDF
57. Ursodiol use is associated with lower prevalence of colonic neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.
- Author
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Tung, Bruce Y., Emond, Mary J., Haggitt, Rodger C., Bronner, Mary P., Kimmey, Michael B., Kowdley, Kris V., Brentnall, Teresa A., Tung, B Y, Emond, M J, Haggitt, R C, Bronner, M P, Kimmey, M B, Kowdley, K V, and Brentnall, T A
- Subjects
COLON cancer ,ANTINEOPLASTIC agents ,COLONOSCOPY ,COLON tumor prevention ,GASTROINTESTINAL agents ,BILE duct diseases ,COLON (Anatomy) ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,PRECANCEROUS conditions ,RESEARCH ,ULCERATIVE colitis ,EVALUATION research ,CROSS-sectional method ,THERAPEUTICS - Abstract
Background: Patients with ulcerative colitis and primary sclerosing cholangitis are at high risk for colonic dysplasia and cancer. This risk approaches 50% after 25 years of colitis. Ursodiol has been shown to protect against development of colorectal neoplasia in animal models.Objective: To assess the relationship between ursodiol use and colonic dysplasia, the precursor to colon cancer, in patients with ulcerative colitis and primary sclerosing cholangitis.Design: Cross-sectional study.Setting: University medical center.Patients: 59 patients with ulcerative colitis and primary sclerosing cholangitis who were undergoing colonoscopic surveillance for colonic dysplasia.Measurements: Use of ursodiol was assessed in all patients. The presence or absence of colonic dysplasia was evaluated by colonoscopic surveillance. Other variables assessed were age at onset and duration of ulcerative colitis; duration of primary sclerosing cholangitis; Child-Pugh classification; and use of sulfasalazine, other 5-aminosalicylic acid preparations, prednisone, cyclosporine, azathioprine, and methotrexate.Results: Ursodiol use was strongly associated with decreased prevalence of colonic dysplasia (odds ratio, 0.18 [95% CI, 0.05 to 0.61]; P = 0.005). The association between dysplasia and ursodiol use remained after adjustment for sex, age at onset of colitis, duration of colitis, duration of sclerosing cholangitis, severity of liver disease, and sulfasalazine use (adjusted odds ratio, 0.14 [CI, 0.03 to 0.64]; P = 0.01). Younger age at onset of colitis was associated with an increased risk for dysplasia.Conclusions: Ursodiol use appears to be associated with a lower frequency of colonic dysplasia in patients with ulcerative colitis and primary sclerosing cholangitis. A randomized trial investigating the chemoprotective effect of ursodiol in patients with ulcerative colitis may be warranted. [ABSTRACT FROM AUTHOR]- Published
- 2001
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58. Relationship between iron concentration and hepatitis C virus RNA level in liver tissue.
- Author
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Cotler, Scott J., Emond, Mary J., Gretch, David R., Wilson, Jeff J., Lin, Masami, Bronner, Mary P., Kowdley, Kris V., Cotler, S J, Emond, M J, Gretch, D R, Wilson, J J, Lin, M, Bronner, M P, and Kowdley, K V
- Published
- 1999
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59. Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer.
- Author
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Brentnall, Teresa A., Bronner, Mary P., Brentnall, T A, Bronner, M P, Byrd, D R, Haggitt, R C, and Kimmey, M B
- Subjects
PANCREATIC diseases ,DYSPLASIA - Abstract
Background: Pancreatic cancer, the fourth most common cause of cancer death in the United States, is hereditary in an estimated 10% of cases. Surveillance of patients with a familial predisposition for pancreatic cancer has not been systematically evaluated.Objective: To develop a surveillance program that can identify and treat patients who have precancerous conditions of the pancreas and a family history of pancreatic cancer.Design: Prospective cohort study.Setting: University medical center.Patients: 14 patients from three kindreds with a history of pancreatic cancer.Interventions: Endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), spiral computed tomography, and serum carcinoembryonic antigen and CA19-9 analysis were performed in all patients. Four affected patients were tested for the K-ras mutation.Main Outcome Measurement: Pancreatic dysplasia was determined by histologic evaluation.Results: Seven of the 14 patients were believed to have dysplasia on the basis of clinical history and abnormalities on endoscopic ultrasonography and ERCP and were referred for pancreatectomy. All 7 patients had histologic evidence of dysplasia in pancreatectomy specimens. Findings on endoscopic ultrasonography were subtle, nonspecific, and similar to those seen in patients with chronic pancreatitis. Findings on ERCP ranged from mild and focal side-branch duct irregularities and small sacculations to main-duct strictures and grapelike clusters of saccules. Some of these changes are typical of chronic pancreatitis, but others are more distinctive. Spiral computed tomography and serum tumor markers had low sensitivity in the detection of pancreatic dysplasia. Analysis for the K-ras mutation yielded positive results in 3 of 4 patients with dysplasia.Conclusions: Thorough screening of patients with a family history of pancreatic cancer is feasible. Clinical data combined with imaging studies (endoscopic ultrasonography and ERCP) can be used to identify high-risk patients who have dysplasia. The role of molecular genetic testing is uncertain at this time. [ABSTRACT FROM AUTHOR]- Published
- 1999
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60. Bridges or barriers to success: the nature of the student experiences in nursing.
- Author
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Bronner M
- Published
- 1982
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61. Estrogen-progesterone therapy for bleeding gastrointestinal telangiectasias in chronic renal failure. An uncontrolled trial.
- Author
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Bronner, Mark H., Pate, Marion B., Cunningham, John T., Marsh, William H., Bronner, M H, Pate, M B, Cunningham, J T, and Marsh, W H
- Subjects
CHRONIC kidney failure ,GASTROINTESTINAL hemorrhage ,PROGESTERONE ,ESTROGEN replacement therapy ,THERAPEUTICS - Abstract
Gastrointestinal telangiectasias cause hemorrhage in patients with chronic renal failure. Therapies using vasoconstrictors, endoscopic application of heat, and surgery have had limited efficacy. Because several reports have suggested that estrogen or estrogen-progesterone therapy may control mucosal bleeding from telangiectasias in patients with hereditary hemorrhagic telangiectasia, we treated seven patients with chronic renal failure and bleeding gastrointestinal telangiectasias with systemic estrogen or estrogen-progesterone in an uncontrolled trial. Bleeding ceased in all patients. Blood transfusion requirements decreased from a mean of 1.2 U/month before treatment to 0.21 U/month after treatment. No significant side effects were noted. Results of this trial indicate the need for controlled investigations of this type of hormonal therapy. [ABSTRACT FROM AUTHOR]
- Published
- 1986
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62. End-stage liver disease without hemochromatosis associated with elevated hepatic iron index
- Author
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Cotler, S. J., Bronner, M. P., Press, R. D., Carlson, T. H., Perkins, J. D., Emond, M. J., and Kowdley, K. V.
- Published
- 1998
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63. Migratory patterns of cloned neural crest melanocytes injected into host chicken embryos.
- Author
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Bronner, M E and Cohen, A M
- Abstract
Cloned quail melanocytes grown in tissue culture for 8 days or more were injected into 2 1/2-day-old chicken embryos. The pigment cells were placed directly into the somitic lumen by means of an injection micropipette. This technique for introducing marked neural crest cells into host embryos causes far less damage than previous methods which require extirpation and replacement of the neural tube. In addition, small numbers of homogeneous cells can be implanted by this procedure. When injected into one of the posterior somites, cultured pigment cells migrated along the ventral neural crest pathway. Three days after injection the melanocytes had migrated ventral to the dorsal root ganglia and prevertebral and primary sympathetic chain ganglia and were seen associated with the adrenal gland and aortic plexi. Melanocytes were frequently found in or adjacent to the gonads and often had migrated as far as the gut.
- Published
- 1979
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64. Regulation of CYP4A1 and Peroxisome Proliferator-activated Receptor Alpha Expression by Interleukin-1 , Interleukin-6, and Dexamethasone in Cultured Fetal Rat Hepatocytes
- Author
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Parmentier, J. H., Schohn, H., Bronner, M., Ferrari, L., Batt, A. M., Dauca, M., and Kremers, P.
- Published
- 1997
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65. Microstructure and charge carrier transport in phthalocyanine based semiconductor blends
- Author
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Andreas Opitz, Wagner, J., Ecker, B., Hörmann, U., Kraus, M., Bronner, M., Brütting, W., Hinderhofer, A., and Schreiber, F.
66. Continental weathering and recovery from ocean nutrient stress during the Early Triassic Biotic Crisis
- Author
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Jochen Knies, Jasmin Schönenberger, Horst Zwingmann, Roelant van der Lelij, Morten Smelror, Per Erik Vullum, Marco Brönner, Christoph Vogt, Ola Fredin, Axel Müller, Stephen E. Grasby, Benoit Beauchamp, Giulio Viola, Knies J., Schonenberger J., Zwingmann H., van der Lelij R., Smelror M., Vullum P.E., Bronner M., Vogt C., Fredin O., Muller A., Grasby S.E., Beauchamp B., and Viola G.
- Subjects
Saprolite ,Early Triassic Biotic Crisi ,Weathering ,General Earth and Planetary Sciences ,Mass extinction ,General Environmental Science - Abstract
Following the latest Permian extinction ∼252 million years ago, normal marine and terrestrial ecosystems did not recover for another 5-9 million years. The driver(s) for the Early Triassic biotic crisis, marked by high atmospheric CO2 concentration, extreme ocean warming, and marine anoxia, remains unclear. Here we constrain the timing of authigenic K-bearing mineral formation extracted from supergene weathering profiles of NW-Pangea by Argon geochronology, to demonstrate that an accelerated hydrological cycle causing intense chemical alteration of the continents occurred between ∼254 and 248 Ma, and continued throughout the Triassic period. We show that enhanced ocean nutrient supply from this intense continental weathering did not trigger increased ocean productivity during the Early Triassic biotic crisis, due to strong thermal ocean stratification off NW Pangea. Nitrogen isotope constraints suggest, instead, that full recovery from ocean nutrient stress, despite some brief amelioration ∼1.5 million years after the latest Permian extinction, did not commence until climate cooling revitalized the global upwelling systems and ocean mixing ∼10 million years after the mass extinctio Continental weathering and recovery from ocean nutrient stress during the Early Triassic Biotic Crisis
- Published
- 2022
67. Spatiotemporal structure of cell fate decisions in murine neural crest
- Author
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Maria Eleni Kastriti, David A. Guertin, G. Giacomo Consalez, Julian Petersen, Ruslan A. Soldatov, Xiaoyan Qian, Yunshi Yang, Tatiana Chontorotzea, Wen Yu Hsiao, Michael L. Piacentino, Markus M. Hilscher, Jean-François Brunet, Matthias Farlik, Viacheslav Dyachuk, Marketa Kaucka, Kaj Fried, Martin Häring, Chika Yokota, Mats Nilsson, Peter V. Kharchenko, Lukas Englmaier, Christoph Bock, Laura Croci, Igor Adameyko, Marianne E. Bronner, Franck Boismoreau, Patrik Ernfors, Natalia Akkuratova, Soldatov, R, Kaucka, M, Kastriti, Me, Petersen, J, Chontorotzea, T, Englmaier, L, Akkuratova, N, Yang, Y, Häring, M, Dyachuk, V, Bock, C, Farlik, M, Piacentino, Ml, Boismoreau, F, Hilscher, Mm, Yokota, C, Qian, X, Nilsson, M, Bronner, M, Croci, L, Hsiao, Wy, Guertin, D, Brunet, Jf, Consalez, Gg, Ernfors, P, Fried, K, Kharchenko, Pv, and Adameyko, I
- Subjects
0301 basic medicine ,Cell type ,Neural Tube ,Ectomesenchyme ,Neurogenesis ,Nerve Tissue Proteins ,Biology ,Cell fate determination ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cranial neural crest ,Single-cell analysis ,Neural Stem Cells ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Cell Lineage ,Neurons ,Multidisciplinary ,Twist-Related Protein 1 ,Neural tube ,Neural crest ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Mesenchymal Stem Cells ,Embryonic stem cell ,Mice, Mutant Strains ,030104 developmental biology ,medicine.anatomical_structure ,Neural Crest ,Single-Cell Analysis ,Neuroscience ,Neuroglia ,030217 neurology & neurosurgery - Abstract
Binary decisions refine fate decisions Neural crest cells develop into tissues ranging from craniofacial bones to peripheral neurons. Combining single-cell RNA sequencing with spatial transcriptomics, Soldatov et al. analyzed how neural crest cells in mouse embryos decide among the various fates available to them (see the Perspective by Mayor). These multipotent cells become biased toward a given fate early on and step through a progression of binary decisions as their fate is refined. Competing fate programs coexist until increased synchronization favors one and repression disfavors the other. Science , this issue p. eaas9536 ; see also p. 937
- Published
- 2019
68. Expanding the genetic and clinical spectrum of Tatton-Brown-Rahman syndrome in a series of 24 French patients.
- Author
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Thomas H, Alix T, Renard É, Renaud M, Wourms J, Zuily S, Leheup B, Geneviève D, Dreumont N, Schmitt E, Bronner M, Muller M, Divoux M, Wandzel M, Ravel JM, Dexheimer M, Becker A, Roth V, Willems M, Coubes C, Vieville G, Devillard F, Schaefer É, Baer S, Piton A, Gérard B, Vincent M, Nizon M, Cogné B, Ruaud L, Couque N, Putoux A, Edery P, Lesca G, Chatron N, Till M, Faivre L, Tran-Mau-Them F, Alessandri JL, Lebrun M, Quélin C, Odent S, Dubourg C, David V, Faoucher M, Mignot C, Keren B, Pisan É, Afenjar A, Julia S, Bieth É, Banneau G, Goldenberg A, Husson T, Campion D, Lecoquierre F, Nicolas G, Charbonnier C, De Saint Martin A, Naudion S, Degoutin M, Rondeau S, Michot C, Cormier-Daire V, Oussalah A, Pourié C, Lambert L, and Bonnet C
- Subjects
- Humans, Male, Female, France epidemiology, Child, Child, Preschool, Adolescent, Germ-Line Mutation genetics, Adult, Phenotype, Young Adult, Growth Disorders genetics, Growth Disorders pathology, Infant, DNA Methyltransferase 3A, Intellectual Disability genetics, Intellectual Disability pathology, DNA (Cytosine-5-)-Methyltransferases genetics
- Abstract
Background: Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as DNA methyltransferase 3 alpha ( DNMT3A )-overgrowth syndrome (DOS), was first described by Tatton-Brown in 2014. This syndrome is characterised by overgrowth, intellectual disability and distinctive facial features and is the consequence of germline loss-of-function variants in DNMT3A , which encodes a DNA methyltransferase involved in epigenetic regulation. Somatic variants of DNMT3A are frequently observed in haematological malignancies, including acute myeloid leukaemia (AML). To date, 100 individuals with TBRS with de novo germline variants have been described. We aimed to further characterise this disorder clinically and at the molecular level in a nationwide series of 24 French patients and to investigate the correlation between the severity of intellectual disability and the type of variant., Methods: We collected genetic and medical information from 24 individuals with TBRS using a questionnaire released through the French National AnDDI-Rares Network., Results: Here, we describe the first nationwide French cohort of 24 individuals with germline likely pathogenic/pathogenic variants in DNMT3A , including 17 novel variants. We confirmed that the main phenotypic features were intellectual disability (100% of individuals), distinctive facial features (96%) and overgrowth (87%). We highlighted novel clinical features, such as hypertrichosis, and further described the neurological features and EEG results., Conclusion: This study of a nationwide cohort of individuals with TBRS confirms previously published data and provides additional information and clarifies clinical features to facilitate diagnosis and improve care. This study adds value to the growing body of knowledge on TBRS and broadens its clinical and molecular spectrum., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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69. Non-invasive laser speckle contrast imaging (LSCI) of extra-embryonic blood vessels in intact avian eggs at early developmental stages.
- Author
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Dong Z, Mahler S, Readhead C, Chen X, Dickson M, Bronner M, and Yang C
- Abstract
Imaging blood vessels in early-stage avian embryos has a wide range of practical applications for developmental biology studies, drug and vaccine testing, and early sex determination. Optical imaging, such as brightfield transmission imaging, offers a compelling solution due to its safe non-ionizing radiation, and operational benefits. However, it comes with challenges, such as eggshell opacity and light scattering. To address these, we have revisited an approach based on laser speckle contrast imaging (LSCI) and demonstrated a high-quality, comprehensive, and non-invasive visualization of blood vessels in few-days-old chicken eggs, with blood vessels as small as 100 µm in diameter (with LSCI profile full-width-at-half-maximum of 275 µm). We present its non-invasive use for monitoring blood flow, measuring the embryo's heartbeat, and determining the embryo's developmental stages using machine learning with 85% accuracy from stage HH15 to HH22. This method can potentially be used for non-invasive longitudinal studies of cardiovascular development and angiogenesis, as well as egg screening for the poultry industry., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)
- Published
- 2024
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70. Low-Iron Diet-Induced Fatty Liver Development Is Microbiota Dependent and Exacerbated by Loss of the Mitochondrial Iron Importer Mitoferrin2.
- Author
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Klag KA, Bell R, Jia X, Seguin A, Maschek JA, Bronner M, Cox JE, Round JL, and Ward DM
- Subjects
- Animals, Female, Male, Mice, Fatty Liver etiology, Insulin Resistance, Iron metabolism, Iron Deficiencies, Iron, Dietary administration & dosage, Lipid Metabolism, Mice, Inbred C57BL, Mice, Knockout, Mitochondria metabolism, Mitochondrial Proteins metabolism, Triglycerides blood, Gastrointestinal Microbiome, Liver metabolism
- Abstract
Iron deficiency is the number one nutritional problem worldwide. Iron uptake is regulated at the intestine and is highly influenced by the gut microbiome. Blood from the intestines drains directly into the liver, informing iron status and gut microbiota status. Changes in either iron or the microbiome are tightly correlated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD). To investigate the underlying mechanisms of the development of MASLD that connect altered iron metabolism and gut microbiota, we compared specific pathogen free (SPF) or germ-free (GF) mice, fed a normal or low-iron diet. SPF mice on a low-iron diet showed reduced serum triglycerides and MASLD. In contrast, GF low-iron diet-fed mice showed increased serum triglycerides and did not develop hepatic steatosis. SPF mice showed significant changes in liver lipid metabolism and increased insulin resistance that was dependent upon the presence of the gut microbiota. We report that total body loss of mitochondrial iron importer Mitoferrin2 ( Mfrn2
- /- ) exacerbated the development of MASLD on a low-iron diet with significant lipid metabolism alterations. Our study demonstrates a clear contribution of the gut microbiome, dietary iron, and Mfrn2 in the development of MASLD and metabolic syndrome.- Published
- 2024
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71. Automating Ground Truth Annotations for Gland Segmentation Through Immunohistochemistry.
- Author
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Kataria T, Rajamani S, Ayubi AB, Bronner M, Jedrzkiewicz J, Knudsen BS, and Elhabian SY
- Subjects
- Humans, Epithelial Cell Adhesion Molecule, Immunohistochemistry, Image Processing, Computer-Assisted, Deep Learning, Colonic Neoplasms
- Abstract
Microscopic evaluation of glands in the colon is of utmost importance in the diagnosis of inflammatory bowel disease and cancer. When properly trained, deep learning pipelines can provide a systematic, reproducible, and quantitative assessment of disease-related changes in glandular tissue architecture. The training and testing of deep learning models require large amounts of manual annotations, which are difficult, time-consuming, and expensive to obtain. Here, we propose a method for automated generation of ground truth in digital hematoxylin and eosin (H&E)-stained slides using immunohistochemistry (IHC) labels. The image processing pipeline generates annotations of glands in H&E histopathology images from colon biopsy specimens by transfer of gland masks from KRT8/18, CDX2, or EPCAM IHC. The IHC gland outlines are transferred to coregistered H&E images for training of deep learning models. We compared the performance of the deep learning models to that of manual annotations using an internal held-out set of biopsy specimens as well as 2 public data sets. Our results show that EPCAM IHC provides gland outlines that closely match manual gland annotations (Dice = 0.89) and are resilient to damage by inflammation. In addition, we propose a simple data sampling technique that allows models trained on data from several sources to be adapted to a new data source using just a few newly annotated samples. The best performing models achieved average Dice scores of 0.902 and 0.89 on Gland Segmentation and Colorectal Adenocarcinoma Gland colon cancer public data sets, respectively, when trained with only 10% of annotated cases from either public cohort. Altogether, the performances of our models indicate that automated annotations using cell type-specific IHC markers can safely replace manual annotations. Automated IHC labels from single-institution cohorts can be combined with small numbers of hand-annotated cases from multi-institutional cohorts to train models that generalize well to diverse data sources., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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72. Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B.
- Author
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Bonnet C, Pellerin D, Roth V, Clément G, Wandzel M, Lambert L, Frismand S, Douarinou M, Grosset A, Bekkour I, Weber F, Girardier F, Robin C, Cacciatore S, Bronner M, Pourié C, Dreumont N, Puisieux S, Iruzubieta P, Dicaire MJ, Evoy F, Rioux MF, Hocquel A, La Piana R, Synofzik M, Houlden H, Danzi MC, Zuchner S, Brais B, and Renaud M
- Subjects
- Humans, Canada, Trinucleotide Repeat Expansion, Friedreich Ataxia genetics, Spinocerebellar Ataxias genetics
- Abstract
Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia. Method comparison showed that capillary electrophoresis of long-range PCR amplification products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, - 2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, - 27.66 to 40.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92 to 1.04]; intercept: 10.62 [95% CI, - 7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, - 41.93 to 39.15]). Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. We also identified 9 French patients (9/53; 17%) and 2 of their relatives who carried an FGF14 (GAA)
≥250 expansion. This novel strategy reliably detected and sized FGF14 GAA expansions, and compared favorably to long-read sequencing., (© 2023. The Author(s).)- Published
- 2023
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73. Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: Report of three families.
- Author
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Becker A, Felici C, Lambert L, de Saint Martin A, Abi-Warde MT, Schaefer E, Zix C, Zamani M, Sadeghian S, Zeighami J, Seifi T, Azizimalamiri R, Shariati G, Galehdari H, Selig M, Ding C, Duerinckx S, Pirson I, Abramowicz M, Clément G, Leheup B, Jonveaux P, Lefort G, Bronner M, Renaud M, and Bonnet C
- Subjects
- Humans, Mutation genetics, Founder Effect, Paraplegia genetics, Pedigree, Phenotype, Intellectual Disability genetics, Spastic Paraplegia, Hereditary genetics, Epilepsy genetics
- Abstract
Bi-allelic variants affecting one of the four genes encoding the AP4 subunits are responsible for the "AP4 deficiency syndrome." Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936). We report on three patients with core features from three unrelated consanguineous families originating from the Middle East. Exome sequencing identified the same homozygous nonsense variant: NM_004722.4(AP4M1):c.1012C>T p.Arg338* (rs146262009). So far, four patients from three other families carrying this homozygous variant have been reported worldwide. We describe their phenotype and compare it to the phenotype of patients with other variants in AP4M1. We construct a shared single-nucleotide polymorphism (SNP) haplotype around AP4M1 in four families and suggest a probable founder effect of Arg338* AP4M1 variant with a common ancestor most likely of Turkish origin., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
- Published
- 2023
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74. Next-generation sequencing: a decisive diagnostic aid for atypical Wilson's disease.
- Author
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Jardel A, Bonnet C, Frismand-Kryloff S, Ravel JM, Schmitt E, Obadia MA, Delassaux S, Bronner M, Poujois A, and Renaud M
- Subjects
- Humans, Copper, High-Throughput Nucleotide Sequencing, Hepatolenticular Degeneration diagnosis, Hepatolenticular Degeneration genetics
- Published
- 2022
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- View/download PDF
75. First report of a short in-frame biallelic deletion removing part of the EGF-like domain calcium-binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C.
- Author
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Ravel JM, Comel M, Wandzel M, Bronner M, Tatopoulos A, Renaud M, Lambert L, Bursztejn AC, and Bonnet C
- Subjects
- Calcium, Cartilage Diseases, DNA, Complementary, Epidermal Growth Factor, Female, Gastrointestinal Diseases, Humans, Infant, Latent TGF-beta Binding Proteins genetics, RNA, Respiratory Tract Diseases, Transforming Growth Factor beta, Urologic Diseases, Cutis Laxa genetics
- Abstract
Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM #613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
- Published
- 2022
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76. Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.
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Himbert C, Stephens WZ, Gigic B, Hardikar S, Holowatyj AN, Lin T, Ose J, Swanson E, Ashworth A, Warby CA, Peoples AR, Nix D, Jedrzkiewicz J, Bronner M, Pickron B, Scaife C, Cohan JN, Schrotz-King P, Habermann N, Boehm J, Hullar M, Figueiredo JC, Toriola AT, Siegel EM, Li CI, Ulrich AB, Shibata D, Boucher K, Huang LC, Schneider M, Round JL, and Ulrich CM
- Abstract
Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients. N=179 patients with colorectal cancer (stages I-IV) were included in the study. Pre-surgery stool samples were used to perform 16S rRNA gene sequencing (Illumina). Physical activity (MET hrs/wk) during the year before diagnosis was assessed by questionnaire and participants were classified as being active vs. inactive based on guidelines. BMI at baseline was abstracted from medical records. Patients were classified into four combinations of physical activity levels/BMI. Lower gut microbial diversity was observed among 'inactive' vs. 'active' patients (Shannon: P =0.01, Simpson: P =0.03), 'obese' vs. 'normal weight' patients (Shannon, Simpson, and Observed species: P =0.02, respectively), and 'overweight/obese/inactive' vs. 'normal weight/active' patients (Shannon: P =0.02, Observed species: P =0.04). Results differed by sex and tumor site. Two phyla and 12 genera (Actinobacteria and Fusobacteria, Adlercreutzia, Anaerococcus, Clostridium, Eubacterium, Mogibacteriaceae, Olsenella, Peptinophilus, Pyramidobacter, RFN20, Ruminococcus, Succinivibrio, Succiniclasticum ) were differentially abundant across physical activity and BMI groups. This is the first evidence for associations of physical activity with gut microbiome diversity and abundances, directly among colorectal cancer patients. Our results indicate that physical activity may offset gut microbiome dysbiosis due to obesity. Alterations in gut microbiota may contribute mechanistically to the energy balance-colorectal cancer link and impact clinical outcomes., Competing Interests: None., (AJCR Copyright © 2022.)
- Published
- 2022
77. uORF-introducing variants in the 5'UTR of the NIPBL gene as a cause of Cornelia de Lange syndrome.
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Coursimault J, Rovelet-Lecrux A, Cassinari K, Brischoux-Boucher E, Saugier-Veber P, Goldenberg A, Lecoquierre F, Drouot N, Richard AC, Vera G, Coutant S, Quenez O, Rolain M, Bonnet C, Bronner M, Lecourtois M, and Nicolas G
- Subjects
- 5' Untranslated Regions, Adolescent, Cell Cycle Proteins genetics, Humans, Male, Open Reading Frames genetics, Phenotype, RNA, Messenger genetics, RNA, Messenger metabolism, De Lange Syndrome diagnosis, De Lange Syndrome genetics
- Abstract
Cornelia de Lange syndrome (CdLS) is a clinically-recognizable rare developmental disorder. About 70% of patients carry a missense or loss-of-function pathogenic variant in the NIPBL gene. We hypothesized that some variants in the 5'-untranslated region (UTR) of NIPBL may create an upstream open reading frame (uORF), putatively leading to a loss of function. We searched for NIPBL 5'-UTR variants potentially introducing uORF by (i) reannotating NGS data of 102 unsolved CdLS patients and (ii) literature and variant databases search. We set up a green fluorescent protein (GFP) reporter assay and studied NIPBL expression in a lymphoblastoid cell line (LCL). We identified two variants introducing a novel ATG codon sequence in the 5'-UTR of NIPBL, both predicted to introduce uORF: a novel c.-457_-456delinsAT de novo mutation in a 15-year-old male with classic CdLS, and a c.-94C>T variant in a published family. Our reporter assay showed a significant decrease of GFP levels in both mutant contexts, with similar levels of messenger RNA (mRNA) as compared to wt constructs. Assessment of LCL of one patient showed consistent results with decreased NIPBL protein and unchanged mRNA levels. 5'-UTR uORF-introducing NIPBL variants may represent a rare source of pathogenic variants in unsolved CdLS patients., (© 2022 Wiley Periodicals LLC.)
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- 2022
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78. Schwann cell precursors represent a neural crest-like state with biased multipotency.
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Kastriti ME, Faure L, Von Ahsen D, Bouderlique TG, Boström J, Solovieva T, Jackson C, Bronner M, Meijer D, Hadjab S, Lallemend F, Erickson A, Kaucka M, Dyachuk V, Perlmann T, Lahti L, Krivanek J, Brunet JF, Fried K, and Adameyko I
- Subjects
- Cell Differentiation physiology, Neurogenesis physiology, Peripheral Nerves, Neural Crest, Schwann Cells metabolism
- Abstract
Schwann cell precursors (SCPs) are nerve-associated progenitors that can generate myelinating and non-myelinating Schwann cells but also are multipotent like the neural crest cells from which they originate. SCPs are omnipresent along outgrowing peripheral nerves throughout the body of vertebrate embryos. By using single-cell transcriptomics to generate a gene expression atlas of the entire neural crest lineage, we show that early SCPs and late migratory crest cells have similar transcriptional profiles characterised by a multipotent "hub" state containing cells biased towards traditional neural crest fates. SCPs keep diverging from the neural crest after being primed towards terminal Schwann cells and other fates, with different subtypes residing in distinct anatomical locations. Functional experiments using CRISPR-Cas9 loss-of-function further show that knockout of the common "hub" gene Sox8 causes defects in neural crest-derived cells along peripheral nerves by facilitating differentiation of SCPs towards sympathoadrenal fates. Finally, specific tumour populations found in melanoma, neurofibroma and neuroblastoma map to different stages of SCP/Schwann cell development. Overall, SCPs resemble migrating neural crest cells that maintain multipotency and become transcriptionally primed towards distinct lineages., (©2022 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2022
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79. Transfer in care and diabetes distress in young adults with type 1 diabetes mellitus.
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Sattoe J, Peeters M, Bronner M, and van Staa A
- Subjects
- Adult, Child, Cross-Sectional Studies, Female, Humans, Quality of Life, Surveys and Questionnaires, Young Adult, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 psychology, Diabetes Mellitus, Type 1 therapy, Self-Management
- Abstract
Introduction: Diabetes distress (DD) is a serious problem in many people with diabetes and is associated with unfavorable clinical and psychosocial outcomes in children and adults. Little is known about DD in young adults (YAs) with type 1 diabetes mellitus (T1DM) who transferred to adult care. This study aimed to explore the differences between YAs with/without DD regarding transfer experiences, self-management and health-related quality of life (HRQoL)., Research Design and Methods: Cross-sectional online questionnaire completed by YAs with T1DM after transfer. DD was measured with the short-form Problem Areas in Diabetes scale. Descriptive analyses were followed by t-tests and χ
2 tests to explore differences between the groups with/without DD. Effect sizes were calculated., Results: Of 164 respondents with mean age 22.7 (±1.56) years, 60.7% was female. The total sample scored low on DD (6.52±4.67; range: 0-17), but 57 (34.8%) had a score ≥8, indicating DD. YAs with DD felt less ready to transfer to adult care than those without DD and scored lower on alliance between pediatric and adult care and reception in adult care. They also reported poorer self-management skills and lower HRQoL in all domains of functioning., Conclusions: More than one-third YAs experienced DD after transfer; this was associated with less favorable transition, self-management and psychosocial outcomes. Transfer in care seems to be a source of DD. Systematic screening on DD and attention for YAs' worries is recommended in both pediatric and adult care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2021
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80. Reprint of: Schwann cell precursors: Where they come from and where they go.
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Solovieva T and Bronner M
- Subjects
- Cell Differentiation physiology, Embryo, Mammalian, Schwann Cells physiology
- Abstract
Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells-the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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81. Author Correction: Guidelines and definitions for research on epithelial-mesenchymal transition.
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Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Campbell K, Cano A, Casanova J, Christofori G, Dedhar S, Derynck R, Ford HL, Fuxe J, García de Herreros A, Goodall GJ, Hadjantonakis AK, Huang RYJ, Kalcheim C, Kalluri R, Kang Y, Khew-Goodall Y, Levine H, Liu J, Longmore GD, Mani SA, Massagué J, Mayor R, McClay D, Mostov KE, Newgreen DF, Nieto MA, Puisieux A, Runyan R, Savagner P, Stanger B, Stemmler MP, Takahashi Y, Takeichi M, Theveneau E, Thiery JP, Thompson EW, Weinberg RA, Williams ED, Xing J, Zhou BP, and Sheng G
- Published
- 2021
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82. Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.
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Eisele Y, Mallea PM, Gigic B, Stephens WZ, Warby CA, Buhrke K, Lin T, Boehm J, Schrotz-King P, Hardikar S, Huang LC, Pickron TB, Scaife CL, Viskochil R, Koelsch T, Peoples AR, Pletneva MA, Bronner M, Schneider M, Ulrich AB, Swanson EA, Toriola AT, Shibata D, Li CI, Siegel EM, Figueiredo J, Janssen KP, Hauner H, Round J, Ulrich CM, Holowatyj AN, and Ose J
- Subjects
- Humans, Microsatellite Instability, Prognosis, Prospective Studies, Colorectal Neoplasms, Fusobacterium nucleatum
- Abstract
Background: Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood., Patients and Methods: We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naïve CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models., Results: Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival., Conclusion: Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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83. Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset.
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Himbert C, Figueiredo JC, Shibata D, Ose J, Lin T, Huang LC, Peoples AR, Scaife CL, Pickron B, Lambert L, Cohan JN, Bronner M, Felder S, Sanchez J, Dessureault S, Coppola D, Hoffman DM, Nasseri YF, Decker RW, Zaghiyan K, Murrell ZA, Hendifar A, Gong J, Firoozmand E, Gangi A, Moore BA, Cologne KG, El-Masry MS, Hinkle N, Monroe J, Mutch M, Bernadt C, Chatterjee D, Sinanan M, Cohen SA, Wallin U, Grady WM, Lampe PD, Reddi D, Krane M, Fichera A, Moonka R, Herpel E, Schirmacher P, Kloor M, von Knebel-Doeberitz M, Nattenmueller J, Kauczor HU, Swanson E, Jedrzkiewicz J, Schmit SL, Gigic B, Ulrich AB, Toriola AT, Siegel EM, Li CI, Ulrich CM, and Hardikar S
- Abstract
Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (<50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients ( n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m
2 , 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III-IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82-3.83) and 2.00 (1.43-2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21-1.98) and 0.56 (0.41-0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.- Published
- 2021
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84. Schwann cell precursors: Where they come from and where they go.
- Author
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Solovieva T and Bronner M
- Subjects
- Animals, Cell Differentiation, Cell Lineage, Humans, Models, Biological, Neuronal Plasticity, Schwann Cells cytology, Stem Cells cytology
- Abstract
Schwann cell precursors (SCPs) are a transient population in the embryo, closely associated with nerves along which they migrate into the periphery of the body. Long considered to be progenitors that only form Schwann cells-the myelinating cells of nerves, current evidence suggests that SCPs have much broader developmental potential. Indeed, different cell marking techniques employed over the past 20 years have identified multiple novel SCP derivatives throughout the body. It is now clear that SCPs represent a multipotent progenitor population, which also display a level of plasticity in response to injury. Moreover, they originate from multiple origins in the embryo and may reflect several distinct subpopulations in terms of molecular identity and fate. Here we review SCP origins, derivatives and plasticity in development, growth and repair., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
85. Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12.
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Meulemans L, Mesman RLS, Caputo SM, Krieger S, Guillaud-Bataille M, Caux-Moncoutier V, Léone M, Boutry-Kryza N, Sokolowska J, Révillion F, Delnatte C, Tubeuf H, Soukarieh O, Bonnet-Dorion F, Guibert V, Bronner M, Bourdon V, Lizard S, Vilquin P, Privat M, Drouet A, Grout C, Calléja FMGR, Golmard L, Vrieling H, Stoppa-Lyonnet D, Houdayer C, Frebourg T, Vreeswijk MPG, Martins A, and Gaildrat P
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Cell Line, Tumor, Embryonic Stem Cells, Exons genetics, Female, Humans, Loss of Function Mutation, Male, Mice, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, Recombinant Proteins genetics, Alternative Splicing, BRCA2 Protein genetics, Genetic Predisposition to Disease, Hereditary Breast and Ovarian Cancer Syndrome genetics
- Abstract
Germline nonsense and canonical splice site variants identified in disease-causing genes are generally considered as loss-of-function (LoF) alleles and classified as pathogenic. However, a fraction of such variants could maintain function through their impact on RNA splicing. To test this hypothesis, we used the alternatively spliced BRCA2 exon 12 (E12) as a model system because its in-frame skipping leads to a potentially functional protein. All E12 variants corresponding to putative LoF variants or predicted to alter splicing ( n = 40) were selected from human variation databases and characterized for their impact on splicing in minigene assays and, when available, in patient lymphoblastoid cell lines. Moreover, a selection of variants was analyzed in a mouse embryonic stem cell-based functional assay. Using these complementary approaches, we demonstrate that a subset of variants, including nonsense variants, induced in-frame E12 skipping through the modification of splice sites or regulatory elements and, consequently, led to an internally deleted but partially functional protein. These data provide evidence, for the first time in a cancer-predisposition gene, that certain presumed null variants can retain function due to their impact on splicing. Further studies are required to estimate cancer risk associated with these hypomorphic variants. More generally, our findings highlight the need to exercise caution in the interpretation of putative LoF variants susceptible to induce in-frame splicing modifications. SIGNIFICANCE: This study presents evidence that certain presumed loss-of-function variants in a cancer predisposition gene can retain function due to their direct impact on RNA splicing., (©2020 American Association for Cancer Research.)
- Published
- 2020
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86. Successful lung cancer EGFR sequencing from DNA extracted from TTF-1 immunohistochemistry slides: a new means to extend insufficient tissue.
- Author
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Deftereos G, Sandoval A, Furtado LV, Bronner M, and Matynia AP
- Subjects
- Adenocarcinoma of Lung chemistry, Adenocarcinoma of Lung pathology, Biomarkers, Tumor analysis, Biopsy, ErbB Receptors genetics, Exons, Humans, Lung Neoplasms chemistry, Lung Neoplasms pathology, Predictive Value of Tests, Proof of Concept Study, Adenocarcinoma of Lung genetics, Biomarkers, Tumor genetics, DNA Mutational Analysis, Immunohistochemistry, Lung Neoplasms genetics, Mutation, Thyroid Nuclear Factor 1 analysis
- Abstract
Lung cancer biopsy material is limited and is used for morphologic diagnosis and immunohistochemical and molecular testing. This can lead to tissue exhaustion, resulting in repeat biopsies (when clinically possible), delayed testing, and increased risks. Consequently, there is a need to optimize preanalytical specimen use for molecular testing. Although hematoxylin/eosin can be used for as a DNA source for molecular testing, little is known regarding the potential use of immunohistochemistry (IHC) slides, as these are subject to harsh conditions that can lead to DNA degradation. Our aim was to evaluate whether DNA extracted from TTF-1 IHC slides, a common stain for lung adenocarcinoma, can be tested for EGFR mutations. Twenty-two lung adenocarcinoma samples (11 EGFR wild type and 11 mutated) were selected. Slides were stained for TTF-1 IHC. Following TTF-1 staining, tissue underwent DNA extraction. Pyrosequencing for mutations in exons 18, 19, 20, and 21 of EGFR was performed, and results were compared to clinical EGFR testing data. All 22 TTF-1 samples produced successful results, and 21 were concordant. Of the 11 originally EGFR-mutated cases, 10 TTF-1 samples showed identical mutations in all exons of interest. One case with an L858R mutation on original testing was negative on sequencing of the TTF-1 sample, possibly due to lower tumor burden on the TTF-1 stained slide. All 11 originally EGFR wild-type cases showed identical results on the TTF-1 samples. TTF-1 IHC slides can be a viable DNA source for molecular testing, especially important in lung biopsies with insufficient material following diagnostic evaluation., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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87. A conserved regulatory program initiates lateral plate mesoderm emergence across chordates.
- Author
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Prummel KD, Hess C, Nieuwenhuize S, Parker HJ, Rogers KW, Kozmikova I, Racioppi C, Brombacher EC, Czarkwiani A, Knapp D, Burger S, Chiavacci E, Shah G, Burger A, Huisken J, Yun MH, Christiaen L, Kozmik Z, Müller P, Bronner M, Krumlauf R, and Mosimann C
- Subjects
- Animals, Embryo, Nonmammalian, Embryonic Induction genetics, Gastrulation genetics, Intravital Microscopy, Zebrafish, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Mesoderm embryology, Zebrafish Proteins genetics
- Abstract
Cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolate a pan-LPM enhancer in the zebrafish-specific draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captures the dynamic LPM emergence as lineage-restricted mesendoderm field. The drl pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncover specific activity of zebrafish-derived drl reporters in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.
- Published
- 2019
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88. Filling in the phylogenetic gaps: Induction, migration, and differentiation of neural crest cells in a squamate reptile, the veiled chameleon (Chamaeleo calyptratus).
- Author
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Diaz RE Jr, Shylo NA, Roellig D, Bronner M, and Trainor PA
- Subjects
- Animals, Biological Evolution, Cell Differentiation, Cell Movement, Lizards genetics, Neural Crest cytology, Phylogeny
- Abstract
Neural crest cells comprise a migratory progenitor cell population that differentiate into cell types such as neurons and glia of the peripheral nervous system, pigment cells, hormone secreting cells in glands, and skeletal and connective tissue in the head, thus making important contributions to most tissues and organs throughout the vertebrate body. The evolutionary appearance of neural crest cells is considered synonymous with the origin of vertebrates and their subsequent diversification and radiation. While the comparative biology of neural crest cells has been studied for a century and a half beginning with their discovery by Wilhelm His in 1868, most of our understanding of their development and function has come from a small number of species. Thus, critical gaps exist in our understanding of how neural crest cells mediate evolution and development. This is particularly true with respect to squamate reptiles (lizards, snakes, amphisbaenians), which account for approximately one-third of all living tetrapods. Here, we present veiled chameleons (Chamaeleo calyptratus) as a model system for studying neural crest cell development in squamates. Chameleons exhibit various morphological specializations associated with an arboreal lifestyle that may have been facilitated through neural crest cells acting as a conduit for evolutionary change., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
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89. Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.
- Author
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Runtsch MC, Nelson MC, Lee SH, Voth W, Alexander M, Hu R, Wallace J, Petersen C, Panic V, Villanueva CJ, Evason KJ, Bauer KM, Mosbruger T, Boudina S, Bronner M, Round JL, Drummond MJ, and O'Connell RM
- Subjects
- Animals, Blood Glucose metabolism, Diet, High-Fat adverse effects, Disease Models, Animal, Female, Gene Expression, Humans, Hyperglycemia genetics, Hyperglycemia metabolism, Hyperglycemia prevention & control, Inflammation genetics, Inflammation metabolism, Insulin blood, Intra-Abdominal Fat metabolism, Intra-Abdominal Fat pathology, Macrophages metabolism, Male, Metabolic Diseases genetics, Metabolic Diseases metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs antagonists & inhibitors, NF-kappa B metabolism, Obesity genetics, Obesity metabolism, Obesity prevention & control, Proto-Oncogene Proteins c-akt genetics, Sirolimus pharmacology, TOR Serine-Threonine Kinases antagonists & inhibitors, TOR Serine-Threonine Kinases genetics, Weight Gain drug effects, Weight Gain genetics, Inflammation prevention & control, Metabolic Diseases prevention & control, MicroRNAs genetics, MicroRNAs metabolism
- Abstract
Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-κB activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways. RNA-sequencing of adipose tissue macrophages demonstrated a role for miR-146a in regulating both inflammation and cellular metabolism, including the mTOR pathway, during obesity. Further, we demonstrate that miR-146a regulates inflammation, cellular respiration and glycolysis in macrophages through a mechanism involving its direct target Traf6. Finally, we found that administration of rapamycin, an inhibitor of mTOR, was able to rescue the obesity phenotype in miR-146a-/- mice. Altogether, our study provides evidence that miR-146a represses inflammation and diet-induced obesity and regulates metabolic processes at the cellular and organismal levels, demonstrating how the combination of diet and miRNA genetics influences obesity and diabetic phenotypes., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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90. Commentary on Le Douarin, 1973 and 1974.
- Author
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Bronner M
- Subjects
- Chimera, Developmental Biology, Neural Crest growth & development
- Published
- 2019
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91. Riding the crest for 150 years!
- Author
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Bronner M
- Subjects
- Animals, Humans, Vertebrates, Neural Crest metabolism, Neural Crest physiology
- Published
- 2018
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92. Diversity of genetic events associated with MLH1 promoter methylation in Lynch syndrome families with heritable constitutional epimutation.
- Author
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Leclerc J, Flament C, Lovecchio T, Delattre L, Ait Yahya E, Baert-Desurmont S, Burnichon N, Bronner M, Cabaret O, Lejeune S, Guimbaud R, Morin G, Mauillon J, Jonveaux P, Laurent-Puig P, Frébourg T, Porchet N, and Buisine MP
- Subjects
- Adult, Alleles, Alu Elements genetics, Colorectal Neoplasms, Hereditary Nonpolyposis epidemiology, Colorectal Neoplasms, Hereditary Nonpolyposis pathology, DNA Methylation genetics, Female, Haplotypes, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Introns genetics, Male, Middle Aged, Mutation, Pedigree, Polymorphism, Single Nucleotide genetics, Promoter Regions, Genetic genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Epigenesis, Genetic, Genetic Predisposition to Disease, MutL Protein Homolog 1 genetics
- Abstract
Purpose: Constitutional epimutations are an alternative to genetic mutations in the etiology of genetic diseases. Some of these epimutations, termed secondary, correspond to the epigenetic effects of cis-acting genetic defects transmitted to the offspring following a Mendelian inheritance pattern. In Lynch syndrome, a few families with such apparently heritable MLH1 epimutations have been reported so far., Methods: We designed a long-range polymerase chain reaction next-generation sequencing strategy to screen MLH1 entire gene and applied it to 4 French families with heritable epimutations and 10 additional patients with no proven transmission of their epimutations., Results: This strategy successfully detected the insertion of an Alu element in MLH1 coding sequence in one family. Two previously unreported MLH1 variants were also identified in other epimutation carriers: a nucleotide substitution within intron 1 and a single-nucleotide deletion in the 5'-UTR. Detection of a partial MLH1 duplication in another family required multiplex ligation-dependent probe amplification technology. We demonstrated the segregation of these variants with MLH1 methylation and studied the functional consequences of these defects on transcription., Conclusion: This is the largest cohort of patients with MLH1 secondary epimutations associated with a broad spectrum of genetic defects. This study provides further insight into the complexity of molecular mechanisms leading to secondary epimutations.
- Published
- 2018
- Full Text
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93. Transcriptome dataset of trunk neural crest cells migrating along the ventral pathway of chick embryos.
- Author
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Murko C, Vieceli FM, and Bronner M
- Abstract
We present a transcriptome dataset generated from migratory chick trunk neural crest cells, which are destined to form components of the peripheral nervous system. Using the Sox10E1 enhancer, which specifically labels neural crest cells migrating on the trunk ventral pathway, we performed fluorescence activated cell sorting (FACS) of electroporated embryos to obtain a pure population of these cells for library preparation and Illumina sequencing. The results provide a list of genes that are enriched in the trunk neural crest. To validate the data, we performed in situ hybridization to visualize expression of selected transcripts.
- Published
- 2018
- Full Text
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94. Full in-frame exon 3 skipping of BRCA2 confers high risk of breast and/or ovarian cancer.
- Author
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Caputo SM, Léone M, Damiola F, Ehlen A, Carreira A, Gaidrat P, Martins A, Brandão RD, Peixoto A, Vega A, Houdayer C, Delnatte C, Bronner M, Muller D, Castera L, Guillaud-Bataille M, Søkilde I, Uhrhammer N, Demontety S, Tubeuf H, Castelain G, Jensen UB, Petitalot A, Krieger S, Lefol C, Moncoutier V, Boutry-Kryza N, Nielsen HR, Sinilnikova O, Stoppa-Lyonnet D, Spurdle AB, Teixeira MR, Coulet F, Thomassen M, and Rouleau E
- Abstract
Germline pathogenic variants in the BRCA2 gene are associated with a cumulative high risk of breast/ovarian cancer. Several BRCA2 variants result in complete loss of the exon-3 at the transcript level. The pathogenicity of these variants and the functional impact of loss of exon 3 have yet to be established. As a collaboration of the COVAR clinical trial group (France), and the ENIGMA consortium for investigating breast cancer gene variants, this study evaluated 8 BRCA2 variants resulting in complete deletion of exon 3. Clinical information for 39 families was gathered from Portugal, France, Denmark and Sweden. Multifactorial likelihood analyses were conducted using information from 293 patients, for 7 out of the 8 variants (including 6 intronic). For all variants combined the likelihood ratio in favor of causality was 4.39*10
25 . These results provide convincing evidence for the pathogenicity of all examined variants that lead to a total exon 3 skipping, and suggest that other variants that result in complete loss of exon 3 at the molecular level could be associated with a high risk of cancer comparable to that associated with classical pathogenic variants in BRCA1 or BRCA2 gene. In addition, our functional study shows, for the first time, that deletion of exon 3 impairs the ability of cells to survive upon Mitomycin-C treatment, supporting lack of function for the altered BRCA2 protein in these cells. Finally, this study demonstrates that any variant leading to expression of only BRCA2 delta-exon 3 will be associated with an increased risk of breast and ovarian cancer., Competing Interests: CONFLICTS OF INTEREST All the other authors declare to have no conflicts of interest.- Published
- 2018
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95. Planar cell polarity signaling coordinates oriented cell division and cell rearrangement in clonally expanding growth plate cartilage.
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Li Y, Li A, Junge J, and Bronner M
- Subjects
- Animals, Chick Embryo, Cartilage cytology, Cell Division, Cell Polarity, Extremities embryology, Growth Plate cytology, Signal Transduction
- Abstract
Both oriented cell divisions and cell rearrangements are critical for proper embryogenesis and organogenesis. However, little is known about how these two cellular events are integrated. Here we examine the linkage between these processes in chick limb cartilage. By combining retroviral-based multicolor clonal analysis with live imaging, the results show that single chondrocyte precursors can generate both single-column and multi-column clones through oriented division followed by cell rearrangements. Focusing on single column formation, we show that this stereotypical tissue architecture is established by a pivot-like process between sister cells. After mediolateral cell division, N-cadherin is enriched in the post-cleavage furrow; then one cell pivots around the other, resulting in stacking into a column. Perturbation analyses demonstrate that planar cell polarity signaling enables cells to pivot in the direction of limb elongation via this N-cadherin-mediated coupling. Our work provides new insights into the mechanisms generating appropriate tissue architecture of limb skeleton.
- Published
- 2017
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96. Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah.
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Jewel Samadder N, Valentine JF, Guthery S, Singh H, Bernstein CN, Wan Y, Wong J, Boucher K, Pappas L, Rowe K, Bronner M, Ulrich CM, Burt RW, Curtin K, and Smith KR
- Subjects
- Adult, Age Factors, Age of Onset, Aged, Cholangitis, Sclerosing complications, Colitis, Ulcerative epidemiology, Colitis, Ulcerative pathology, Colon pathology, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Crohn Disease epidemiology, Crohn Disease pathology, Female, Humans, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Sex Factors, Utah epidemiology, Colitis, Ulcerative complications, Colorectal Neoplasms etiology, Crohn Disease complications
- Abstract
Background and Aims: The molecular, endoscopic, and histological features of IBD-associated CRC differ from sporadic CRC. The objective of this study was to describe the prevalence, clinical features, and prognosis of IBD-associated CRC compared to patients with sporadic CRC in a US statewide population-based cohort., Methods: All newly diagnosed cases of CRC between 1996 and 2011 were obtained from Utah Cancer Registry. IBD was identified using a previously validated algorithm, from statewide databases of Intermountain Healthcare, University of Utah Health Sciences, and the Utah Population Database. Logistic regression was performed to identify risk factors associated with IBD-associated cancer and Cox regression for differences in survival., Results: Among 12,578 patients diagnosed with CRC, 101 (0.8%) had a prior history of IBD (61 ulcerative colitis and 40 Crohn's disease). The mean age at CRC diagnosis was greater for patients without IBD than those with IBD (67.1 vs 52.8 years, P < 0.001). Individuals with IBD-associated CRC were more likely to be men (odds ratio [OR] 1.90, 95% CI 1.23-2.92), aged less than 65 years (OR 6.77, 95% CI 4.06-11.27), and have CRC located in the proximal colon (OR 2.79, 95% CI 1.85-4.20) than those with sporadic CRC. Nearly 20% of the IBD-associated CRCs had evidence of primary sclerosing cholangitis. After adjustment for age, gender, and stage at diagnosis, the excess hazard of death after CRC diagnosis was 1.7 times higher in IBD than in non-IBD patients (95% CI 1.27-2.33)., Conclusions: The features of patients with CRC and IBD differ significantly from those without IBD and may be associated with increased mortality.
- Published
- 2017
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97. BRCA Share: A Collection of Clinical BRCA Gene Variants.
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Béroud C, Letovsky SI, Braastad CD, Caputo SM, Beaudoux O, Bignon YJ, Bressac-De Paillerets B, Bronner M, Buell CM, Collod-Béroud G, Coulet F, Derive N, Divincenzo C, Elzinga CD, Garrec C, Houdayer C, Karbassi I, Lizard S, Love A, Muller D, Nagan N, Nery CR, Rai G, Revillion F, Salgado D, Sévenet N, Sinilnikova O, Sobol H, Stoppa-Lyonnet D, Toulas C, Trautman E, Vaur D, Vilquin P, Weymouth KS, Willis A, Eisenberg M, and Strom CM
- Subjects
- Data Curation, Female, Genetic Predisposition to Disease, Humans, Mutation, BRCA1 Protein genetics, BRCA2 Protein genetics, Breast Neoplasms genetics, Databases, Factual economics, Ovarian Neoplasms genetics
- Abstract
As next-generation sequencing increases access to human genetic variation, the challenge of determining clinical significance of variants becomes ever more acute. Germline variants in the BRCA1 and BRCA2 genes can confer substantial lifetime risk of breast and ovarian cancer. Assessment of variant pathogenicity is a vital part of clinical genetic testing for these genes. A database of clinical observations of BRCA variants is a critical resource in that process. This article describes BRCA Share™, a database created by a unique international alliance of academic centers and commercial testing laboratories. By integrating the content of the Universal Mutation Database generated by the French Unicancer Genetic Group with the testing results of two large commercial laboratories, Quest Diagnostics and Laboratory Corporation of America (LabCorp), BRCA Share™ has assembled one of the largest publicly accessible collections of BRCA variants currently available. Although access is available to academic researchers without charge, commercial participants in the project are required to pay a support fee and contribute their data. The fees fund the ongoing curation effort, as well as planned experiments to functionally characterize variants of uncertain significance. BRCA Share™ databases can therefore be considered as models of successful data sharing between private companies and the academic world., (© 2016 WILEY PERIODICALS, INC.)
- Published
- 2016
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98. Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk.
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Baert-Desurmont S, Charbonnier F, Houivet E, Ippolito L, Mauillon J, Bougeard M, Abadie C, Malka D, Duffour J, Desseigne F, Colas C, Pujol P, Lejeune S, Dugast C, Buecher B, Faivre L, Leroux D, Gesta P, Coupier I, Guimbaud R, Berthet P, Manouvrier S, Cauchin E, Prieur F, Laurent-Puig P, Lebrun M, Jonveaux P, Chiesa J, Caron O, Morin-Meschin ME, Polycarpe-Osaer F, Giraud S, Zaanan A, Bonnet D, Mansuy L, Bonadona V, El Chehadeh S, Duhoux F, Gauthier-Villars M, Saurin JC, Collonge-Rame MA, Brugières L, Wang Q, Bressac-de Paillerets B, Rey JM, Toulas C, Buisine MP, Bronner M, Sokolowska J, Hardouin A, Cailleux AF, Sebaoui H, Blot J, Tinat J, Benichou J, and Frebourg T
- Subjects
- Adult, Alleles, Case-Control Studies, Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology, Female, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Genotyping Techniques, Humans, Male, Middle Aged, Odds Ratio, Prospective Studies, Risk Factors, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 8, Colorectal Neoplasms genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
- Abstract
To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's χ(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P<0.0001) cumulative effect of the at-risk alleles or genotypes with OR at 1.62 (CI: 1.10-2.37), 2.09 (CI: 1.43-3.07), 2.87 (CI: 1.76-4.70) and 3.88 (CI: 1.72-8.76) for 1, 2, 3 and at least 4 at-risk alleles, respectively, and OR at 1.71 (CI: 1.18-2.46), 2.29 (CI: 1.55-3.38) and 6.21 (CI: 2.67-14.42) for 1, 2 and 3 at-risk genotypes, respectively. Combination of SNPs may therefore explain a fraction of clinical situations suggestive of an increased risk for CRC.
- Published
- 2016
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99. Digitally guided microdissection aids somatic mutation detection in difficult to dissect tumors.
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Geiersbach K, Adey N, Welker N, Elsberry D, Malmberg E, Edwards S, Downs-Kelly E, Salama M, and Bronner M
- Subjects
- DNA, Neoplasm genetics, DNA, Neoplasm isolation & purification, Humans, Mass Spectrometry methods, Microdissection methods, Mutation, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Paraffin Embedding methods, Tissue Fixation methods
- Abstract
Molecular genetic testing on formalin fixed, paraffin embedded (FFPE) tumors frequently requires dissection of tumor from tissue sections mounted on glass slides. In a process referred to as "manual macrodissection," the pathologist reviews an H&E stained slide at the light microscope and marks areas for dissection, and then the laboratory performs manual dissection from adjacent sections without the aid of a microscope, using the marked reference H&E slide as a guide. Manual macrodissection may be inadequate for tissue sections with low tumor content. We compared manual macrodissection to a new method, digitally guided microdissection, on a series of 32 FFPE pancreatic cancer samples. KRAS hotspot mutation profiling was performed using the Sequenom MassARRAY system (Agena Bioscience). Digitally guided microdissection was performed on multiple smaller areas of high tumor content selected from within the larger areas marked for manual macrodissection. The KRAS mutant allele fraction and estimated neoplastic cellularity were significantly higher in samples obtained by digitally guided microdissection (p < 0.01), and 7 of the 32 samples (22%) showed a detectable mutation only with digitally guided microdissection. DNA quality and yield per cubic millimeter of dissected tissue were similar for both dissection methods. These results indicate a significant improvement in tumor content achievable with digitally guided microdissection., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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100. Animal models for studying neural crest development: is the mouse different?
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Barriga EH, Trainor PA, Bronner M, and Mayor R
- Subjects
- Animals, Chick Embryo, Gene Expression Regulation, Developmental genetics, Mice, Species Specificity, Xenopus, Zebrafish, Gene Expression Regulation, Developmental physiology, Gene Knockout Techniques methods, Models, Animal, Neural Crest embryology, Phenotype
- Abstract
The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems., (© 2015. Published by The Company of Biologists Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
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