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514 results on '"Capella, G."'

1. Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/ Polyposis Variant Curation Expert Panel

Author

Spier, I, Yin, X, Richardson, M, Pineda, M, Laner, A, Ritter, D, Boyle, J, Mur, P, Hansen, TVO, Shi, X, Mahmood, K, Plazzer, J-P, Ognedal, E, Nordling, M, Farrington, SM, Yamamoto, G, Baert-Desurmont, S, Martins, A, Borras, E, Tops, C, Webb, E, Beshay, V, Genuardi, M, Pesaran, T, Capella, G, Tavtigian, S, Latchford, A, Frayling, IM, Plon, SE, Greenblatt, M, Macrae, FA, Aretz, S, Spier, I, Yin, X, Richardson, M, Pineda, M, Laner, A, Ritter, D, Boyle, J, Mur, P, Hansen, TVO, Shi, X, Mahmood, K, Plazzer, J-P, Ognedal, E, Nordling, M, Farrington, SM, Yamamoto, G, Baert-Desurmont, S, Martins, A, Borras, E, Tops, C, Webb, E, Beshay, V, Genuardi, M, Pesaran, T, Capella, G, Tavtigian, S, Latchford, A, Frayling, IM, Plon, SE, Greenblatt, M, Macrae, FA, and Aretz, S

Abstract

PURPOSE: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. METHODS: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. RESULTS: The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). CONCLUSION: The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use.

Published
2024

2. Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

Author

Dominguez-Valentin, M, Haupt, S, Seppälä, T, Sampson, J, Sunde, L, Bernstein, I, Jenkins, M, Engel, C, Aretz, S, Nielsen, M, Capella, G, Balaguer, F, Evans, D, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Dębniak, T, Fruscio, R, Lopez-Koestner, F, Alvarez-Valenzuela, K, Katz, L, Laish, I, Vainer, E, Vaccaro, C, Carraro, D, Monahan, K, Half, E, Stakelum, A, Winter, D, Kennelly, R, Gluck, N, Sheth, H, Abu-Freha, N, Greenblatt, M, Rossi, B, Bohorquez, M, Cavestro, G, Lino-Silva, L, Horisberger, K, Tibiletti, M, Nascimento, I, Thomas, H, Rossi, N, Apolinário da Silva, L, Zaránd, A, Ruiz-Bañobre, J, Heuveline, V, Mecklin, J, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepistö, A, Peltomäki, P, Therkildsen, C, Madsen, M, Burgdorf, S, Hopper, J, Win, A, Haile, R, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, P, Figueiredo, J, Buchanan, D, Thibodeau, S, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schröck, E, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hüneburg, R, Redler, S, Büttner, R, Weitz, J, Pineda, M, Duenas, N, Vidal, J, Moreira, L, Sánchez, A, Hovig, E, Nakken, S, Green, K, Lalloo, F, Hill, J, Crosbie, E, Mints, M, Goldberg, Y, Dominguez-Valentin M., Haupt S., Seppälä T. T., Sampson J. R., Sunde L., Bernstein I., Jenkins M. A., Engel C., Aretz S., Nielsen M., Capella G., Balaguer F., Evans D. G., Burn J., Holinski-Feder E., Bertario L., Bonanni B., Lindblom A., Levi Z., Macrae F., Winship I., Plazzer J. P., Sijmons R., Laghi L., Della Valle A., Heinimann K., Dębniak T., Fruscio R., Lopez-Koestner F., Alvarez-Valenzuela K., Katz L. H., Laish I., Vainer E., Vaccaro C., Carraro D. M., Monahan K., Half E., Stakelum A., Winter D., Kennelly R., Gluck N., Sheth H., Abu-Freha N., Greenblatt M., Rossi B. M., Bohorquez M., Cavestro G. M., Lino-Silva L. S., Horisberger K., Tibiletti M. G., Nascimento I. d., Thomas H., Rossi N. T., Apolinário da Silva L., Zaránd A., Ruiz-Bañobre J., Heuveline V., Mecklin J. P., Pylvänäinen K., Renkonen-Sinisalo L., Lepistö A., Peltomäki P., Therkildsen C., Madsen M. G., Burgdorf S. K., Hopper J. L., Win A. K., Haile R. W., Lindor N., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J., Buchanan D. D., Thibodeau S. N., von Knebel Doeberitz M., Loeffler M., Rahner N., Schröck E., Steinke-Lange V., Schmiegel W., Vangala D., Perne C., Hüneburg R., Redler S., Büttner R., Weitz J., Pineda M., Duenas N., Vidal J. B., Moreira L., Sánchez A., Hovig E., Nakken S., Green K., Lalloo F., Hill J., Crosbie E., Mints M., Goldberg Y., Dominguez-Valentin, M, Haupt, S, Seppälä, T, Sampson, J, Sunde, L, Bernstein, I, Jenkins, M, Engel, C, Aretz, S, Nielsen, M, Capella, G, Balaguer, F, Evans, D, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Dębniak, T, Fruscio, R, Lopez-Koestner, F, Alvarez-Valenzuela, K, Katz, L, Laish, I, Vainer, E, Vaccaro, C, Carraro, D, Monahan, K, Half, E, Stakelum, A, Winter, D, Kennelly, R, Gluck, N, Sheth, H, Abu-Freha, N, Greenblatt, M, Rossi, B, Bohorquez, M, Cavestro, G, Lino-Silva, L, Horisberger, K, Tibiletti, M, Nascimento, I, Thomas, H, Rossi, N, Apolinário da Silva, L, Zaránd, A, Ruiz-Bañobre, J, Heuveline, V, Mecklin, J, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepistö, A, Peltomäki, P, Therkildsen, C, Madsen, M, Burgdorf, S, Hopper, J, Win, A, Haile, R, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, P, Figueiredo, J, Buchanan, D, Thibodeau, S, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schröck, E, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hüneburg, R, Redler, S, Büttner, R, Weitz, J, Pineda, M, Duenas, N, Vidal, J, Moreira, L, Sánchez, A, Hovig, E, Nakken, S, Green, K, Lalloo, F, Hill, J, Crosbie, E, Mints, M, Goldberg, Y, Dominguez-Valentin M., Haupt S., Seppälä T. T., Sampson J. R., Sunde L., Bernstein I., Jenkins M. A., Engel C., Aretz S., Nielsen M., Capella G., Balaguer F., Evans D. G., Burn J., Holinski-Feder E., Bertario L., Bonanni B., Lindblom A., Levi Z., Macrae F., Winship I., Plazzer J. P., Sijmons R., Laghi L., Della Valle A., Heinimann K., Dębniak T., Fruscio R., Lopez-Koestner F., Alvarez-Valenzuela K., Katz L. H., Laish I., Vainer E., Vaccaro C., Carraro D. M., Monahan K., Half E., Stakelum A., Winter D., Kennelly R., Gluck N., Sheth H., Abu-Freha N., Greenblatt M., Rossi B. M., Bohorquez M., Cavestro G. M., Lino-Silva L. S., Horisberger K., Tibiletti M. G., Nascimento I. d., Thomas H., Rossi N. T., Apolinário da Silva L., Zaránd A., Ruiz-Bañobre J., Heuveline V., Mecklin J. P., Pylvänäinen K., Renkonen-Sinisalo L., Lepistö A., Peltomäki P., Therkildsen C., Madsen M. G., Burgdorf S. K., Hopper J. L., Win A. K., Haile R. W., Lindor N., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J., Buchanan D. D., Thibodeau S. N., von Knebel Doeberitz M., Loeffler M., Rahner N., Schröck E., Steinke-Lange V., Schmiegel W., Vangala D., Perne C., Hüneburg R., Redler S., Büttner R., Weitz J., Pineda M., Duenas N., Vidal J. B., Moreira L., Sánchez A., Hovig E., Nakken S., Green K., Lalloo F., Hill J., Crosbie E., Mints M., and Goldberg Y.

Abstract

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We ackno

Published
2023

4. Ultra-selection of metastatic colorectal cancer patients using next-generation sequencing to improve clinical efficacy of anti-EGFR therapy

Author

Vidal, J., Bellosillo, B., Santos Vivas, C., García-Alfonso, P., Carrato, A., Cano, M.T., García-Carbonero, R., Élez, E., Losa, F., Massutí, B., Valladares-Ayerbes, M., Viéitez, J.M., Manzano, J.L., Azuara, D., Gallego, J., Pairet, S., Capellá, G., Salazar, R., Tabernero, J., Aranda, E., and Montagut, C.

Published
2019
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5. A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Author

Denomme-Pichon A. -S., Bruel A. -L., Duffourd Y., Safraou H., Thauvin-Robinet C., Tran Mau-Them F., Philippe C., Vitobello A., Jean-Marcais N., Moutton S., Thevenon J., Faivre L., Matalonga L., de Boer E., Gilissen C., Hoischen A., Kleefstra T., Pfundt R., de Vries B. B. A., Willemsen M. H., Vissers L. E. L. M., Jackson A., Banka S., Clayton-Smith J., Benetti E., Fallerini C., Renieri A., Ciolfi A., Dallapiccola B., Pizzi S., Radio F. C., Tartaglia M., Ellwanger K., Graessner H., Haack T. B., Zurek B., Havlovicova M., Macek M., Ryba L., Schwarz M., Votypka P., Lopez-Martin E., Posada M., Mencarelli M. A., Rooryck C., Trimouille A., Verloes A., Abbott K. M., Kerstjens M., Martin E. L., Maystadt I., Morleo M., Nigro V., Pinelli M., Riess O., Agathe J. -M. D. S., Santen G. W. E., Thauvin C., Torella A., Vissers L., Zguro K., Boer E. D., Cohen E., Danis D., Gao F., Horvath R., Johari M., Johanson L., Li S., Morsy H., Nelson I., Paramonov I., te Paske I. B. A. W., Robinson P., Savarese M., Steyaert W., Topf A., van der Velde J. K., Vandrovcova J., Ossowski S., Demidov G., Sturm M., Schulze-Hentrich J. M., Schule R., Xu J., Kessler C., Wayand M., Synofzik M., Wilke C., Traschutz A., Schols L., Hengel H., Lerche H., Kegele J., Heutink P., Brunner H., Scheffer H., Hoogerbrugge N., 't Hoen P. A. C., Sablauskas K., de Voer R. M., Kamsteeg E. -J., van de Warrenburg B., van Os N., Paske I. T., Janssen E., Steehouwer M., Yaldiz B., Brookes A. J., Veal C., Gibson S., Maddi V., Mehtarizadeh M., Riaz U., Warren G., Dizjikan F. Y., Shorter T., Straub V., Bettolo C. M., Manera J. D., Hambleton S., Engelhardt K., Alexander E., Peyron C., Pelissier A., Beltran S., Gut I. G., Laurie S., Piscia D., Papakonstantinou A., Bullich G., Corvo A., Fernandez-Callejo M., Hernandez C., Pico D., Lochmuller H., Gumus G., Bros-Facer V., Rath A., Hanauer M., Lagorce D., Hongnat O., Chahdil M., Lebreton E., Stevanin G., Durr A., Davoine C. -S., Guillot-Noel L., Heinzmann A., Coarelli G., Bonne G., Evangelista T., Allamand V., Ben Yaou R., Metay C., Eymard B., Atalaia A., Stojkovic T., Turnovec M., Thomasova D., Kremlikova R. P., Frankova V., Liskova P., Dolezalova P., Parkinson H., Keane T., Freeberg M., Thomas C., Spalding D., Robert G., Costa A., Patch C., Hanna M., Houlden H., Reilly M., Efthymiou S., Cali E., Magrinelli F., Sisodiya S. M., Rohrer J., Muntoni F., Zaharieva I., Sarkozy A., Timmerman V., Baets J., de Vries G., De Winter J., Beijer D., de Jonghe P., Van de Vondel L., De Ridder W., Weckhuysen S., Mutarelli M., Varavallo A., Banfi S., Musacchia F., Piluso G., Ferlini A., Selvatici R., Gualandi F., Bigoni S., Rossi R., Neri M., Aretz S., Spier I., Sommer A. K., Peters S., Oliveira C., Pelaez J. G., Matos A. R., Jose C. S., Ferreira M., Gullo I., Fernandes S., Garrido L., Ferreira P., Carneiro F., Swertz M. A., Johansson L., van der Vries G., Neerincx P. B., Ruvolo D., Kerstjens Frederikse W. S., Zonneveld-Huijssoon E., Roelofs-Prins D., van Gijn M., Kohler S., Metcalfe A., Drunat S., Heron D., Mignot C., Keren B., Lacombe D., Capella G., Valle L., Holinski-Feder E., Laner A., Steinke-Lange V., Cilio M. -R., Carpancea E., Depondt C., Lederer D., Sznajer Y., Duerinckx S., Mary S., Macaya A., Cazurro-Gutierrez A., Perez-Duenas B., Munell F., Jarava C. F., Maso L. B., Marce-Grau A., Colobran R., Hackman P., Udd B., Hemelsoet D., Dermaut B., Schuermans N., Poppe B., Verdin H., Osorio A. N., Depienne C., Roos A., Cordts I., Deschauer M., Striano P., Zara F., Riva A., Iacomino M., Uva P., Scala M., Scudieri P., Basak A. N., Claeys K., Boztug K., Haimel M., W. E G., Ruivenkamp C. A. L., Natera de Benito D., Thompson R., Polavarapu K., Grimbacher B., Zaganas I., Kokosali E., Lambros M., Evangeliou A., Spilioti M., Kapaki E., Bourbouli M., Balicza P., Molnar M. J., De la Paz M. P., Sanchez E. B., Delgado B. M., Alonso Garcia de la Rosa F. J., Schrock E., Rump A., Mei D., Vetro A., Balestrini S., Guerrini R., Chinnery P. F., Ratnaike T., Schon K., Maver A., Peterlin B., Munchau A., Lohmann K., Herzog R., Pauly M., May P., Beeson D., Cossins J., Furini S., Afenjar A., Goldenberg A., Masurel A., Phan A., Dieux-Coeslier A., Fargeot A., Guerrot A. -M., Toutain A., Molin A., Sorlin A., Putoux A., Jouret B., Laudier B., Demeer B., Doray B., Bonniaud B., Isidor B., Gilbert-Dussardier B., Leheup B., Reversade B., Paul C., Vincent-Delorme C., Neiva C., Poirsier C., Quelin C., Chiaverini C., Coubes C., Francannet C., Colson C., Desplantes C., Wells C., Goizet C., Sanlaville D., Amram D., Lehalle D., Genevieve D., Gaillard D., Zivi E., Sarrazin E., Steichen E., Schaefer E., Lacaze E., Jacquemin E., Bongers E., Kilic E., Colin E., Giuliano F., Prieur F., Laffargue F., Morice-Picard F., Petit F., Cartault F., Feillet F., Baujat G., Morin G., Diene G., Journel H., Perthus I., Lespinasse J., Alessandri J. -L., Amiel J., Martinovic J., Delanne J., Albuisson J., Lambert L., Perrin L., Ousager L. B., Van Maldergem L., Pinson L., Ruaud L., Samimi M., Bournez M., Bonnet-Dupeyron M. N., Vincent M., Jacquemont M. -L., Cordier-Alex M. -P., Gerard-Blanluet M., Willems M., Spodenkiewicz M., Doco-Fenzy M., Rossi M., Renaud M., Fradin M., Mathieu M., Holder-Espinasse M. H., Houcinat N., Hanna N., Leperrier N., Chassaing N., Philip N., Boute O., Van Kien P. K., Parent P., Bitoun P., Sarda P., Vabres P., Jouk P. -S., Touraine R., El Chehadeh S., Whalen S., Marlin S., Passemard S., Grotto S., Bellanger S. A., Blesson S., Nambot S., Naudion S., Lyonnet S., Odent S., Attie-Bitach T., Busa T., Drouin-Garraud V., Layet V., Bizaoui V., Cusin V., Capri Y., Alembik Y., Unión Europea. Comisión Europea. H2020, Unión Europea. Comisión Europea. 7 Programa Marco, Instituto de Salud Carlos III, Instituto Nacional de Bioinformatica (España), Ministry of Health (República Checa), Ministry of Education, Youth and Sports (República Checa), Denomme-Pichon, A. -S., Bruel, A. -L., Duffourd, Y., Safraou, H., Thauvin-Robinet, C., Tran Mau-Them, F., Philippe, C., Vitobello, A., Jean-Marcais, N., Moutton, S., Thevenon, J., Faivre, L., Matalonga, L., de Boer, E., Gilissen, C., Hoischen, A., Kleefstra, T., Pfundt, R., de Vries, B. B. A., Willemsen, M. H., Vissers, L. E. L. M., Jackson, A., Banka, S., Clayton-Smith, J., Benetti, E., Fallerini, C., Renieri, A., Ciolfi, A., Dallapiccola, B., Pizzi, S., Radio, F. C., Tartaglia, M., Ellwanger, K., Graessner, H., Haack, T. B., Zurek, B., Havlovicova, M., Macek, M., Ryba, L., Schwarz, M., Votypka, P., Lopez-Martin, E., Posada, M., Mencarelli, M. A., Rooryck, C., Trimouille, A., Verloes, A., Abbott, K. M., Kerstjens, M., Martin, E. L., Maystadt, I., Morleo, M., Nigro, V., Pinelli, M., Riess, O., Agathe, J. -M. D. S., Santen, G. W. E., Thauvin, C., Torella, A., Vissers, L., Zguro, K., Boer, E. D., Cohen, E., Danis, D., Gao, F., Horvath, R., Johari, M., Johanson, L., Li, S., Morsy, H., Nelson, I., Paramonov, I., te Paske, I. B. A. W., Robinson, P., Savarese, M., Steyaert, W., Topf, A., van der Velde, J. K., Vandrovcova, J., Ossowski, S., Demidov, G., Sturm, M., Schulze-Hentrich, J. M., Schule, R., Xu, J., Kessler, C., Wayand, M., Synofzik, M., Wilke, C., Traschutz, A., Schols, L., Hengel, H., Lerche, H., Kegele, J., Heutink, P., Brunner, H., Scheffer, H., Hoogerbrugge, N., 't Hoen, P. A. C., Sablauskas, K., de Voer, R. M., Kamsteeg, E. -J., van de Warrenburg, B., van Os, N., Paske, I. T., Janssen, E., Steehouwer, M., Yaldiz, B., Brookes, A. J., Veal, C., Gibson, S., Maddi, V., Mehtarizadeh, M., Riaz, U., Warren, G., Dizjikan, F. Y., Shorter, T., Straub, V., Bettolo, C. M., Manera, J. D., Hambleton, S., Engelhardt, K., Alexander, E., Peyron, C., Pelissier, A., Beltran, S., Gut, I. G., Laurie, S., Piscia, D., Papakonstantinou, A., Bullich, G., Corvo, A., Fernandez-Callejo, M., Hernandez, C., Pico, D., Lochmuller, H., Gumus, G., Bros-Facer, V., Rath, A., Hanauer, M., Lagorce, D., Hongnat, O., Chahdil, M., Lebreton, E., Stevanin, G., Durr, A., Davoine, C. -S., Guillot-Noel, L., Heinzmann, A., Coarelli, G., Bonne, G., Evangelista, T., Allamand, V., Ben Yaou, R., Metay, C., Eymard, B., Atalaia, A., Stojkovic, T., Turnovec, M., Thomasova, D., Kremlikova, R. P., Frankova, V., Liskova, P., Dolezalova, P., Parkinson, H., Keane, T., Freeberg, M., Thomas, C., Spalding, D., Robert, G., Costa, A., Patch, C., Hanna, M., Houlden, H., Reilly, M., Efthymiou, S., Cali, E., Magrinelli, F., Sisodiya, S. M., Rohrer, J., Muntoni, F., Zaharieva, I., Sarkozy, A., Timmerman, V., Baets, J., de Vries, G., De Winter, J., Beijer, D., de Jonghe, P., Van de Vondel, L., De Ridder, W., Weckhuysen, S., Mutarelli, M., Varavallo, A., Banfi, S., Musacchia, F., Piluso, G., Ferlini, A., Selvatici, R., Gualandi, F., Bigoni, S., Rossi, R., Neri, M., Aretz, S., Spier, I., Sommer, A. K., Peters, S., Oliveira, C., Pelaez, J. G., Matos, A. R., Jose, C. S., Ferreira, M., Gullo, I., Fernandes, S., Garrido, L., Ferreira, P., Carneiro, F., Swertz, M. A., Johansson, L., van der Vries, G., Neerincx, P. B., Ruvolo, D., Kerstjens Frederikse, W. S., Zonneveld-Huijssoon, E., Roelofs-Prins, D., van Gijn, M., Kohler, S., Metcalfe, A., Drunat, S., Heron, D., Mignot, C., Keren, B., Lacombe, D., Capella, G., Valle, L., Holinski-Feder, E., Laner, A., Steinke-Lange, V., Cilio, M. -R., Carpancea, E., Depondt, C., Lederer, D., Sznajer, Y., Duerinckx, S., Mary, S., Macaya, A., Cazurro-Gutierrez, A., Perez-Duenas, B., Munell, F., Jarava, C. F., Maso, L. B., Marce-Grau, A., Colobran, R., Hackman, P., Udd, B., Hemelsoet, D., Dermaut, B., Schuermans, N., Poppe, B., Verdin, H., Osorio, A. N., Depienne, C., Roos, A., Cordts, I., Deschauer, M., Striano, P., Zara, F., Riva, A., Iacomino, M., Uva, P., Scala, M., Scudieri, P., Basak, A. N., Claeys, K., Boztug, K., Haimel, M., W. E, G., Ruivenkamp, C. A. L., Natera de Benito, D., Thompson, R., Polavarapu, K., Grimbacher, B., Zaganas, I., Kokosali, E., Lambros, M., Evangeliou, A., Spilioti, M., Kapaki, E., Bourbouli, M., Balicza, P., Molnar, M. J., De la Paz, M. P., Sanchez, E. B., Delgado, B. M., Alonso Garcia de la Rosa, F. J., Schrock, E., Rump, A., Mei, D., Vetro, A., Balestrini, S., Guerrini, R., Chinnery, P. F., Ratnaike, T., Schon, K., Maver, A., Peterlin, B., Munchau, A., Lohmann, K., Herzog, R., Pauly, M., May, P., Beeson, D., Cossins, J., Furini, S., Afenjar, A., Goldenberg, A., Masurel, A., Phan, A., Dieux-Coeslier, A., Fargeot, A., Guerrot, A. -M., Toutain, A., Molin, A., Sorlin, A., Putoux, A., Jouret, B., Laudier, B., Demeer, B., Doray, B., Bonniaud, B., Isidor, B., Gilbert-Dussardier, B., Leheup, B., Reversade, B., Paul, C., Vincent-Delorme, C., Neiva, C., Poirsier, C., Quelin, C., Chiaverini, C., Coubes, C., Francannet, C., Colson, C., Desplantes, C., Wells, C., Goizet, C., Sanlaville, D., Amram, D., Lehalle, D., Genevieve, D., Gaillard, D., Zivi, E., Sarrazin, E., Steichen, E., Schaefer, E., Lacaze, E., Jacquemin, E., Bongers, E., Kilic, E., Colin, E., Giuliano, F., Prieur, F., Laffargue, F., Morice-Picard, F., Petit, F., Cartault, F., Feillet, F., Baujat, G., Morin, G., Diene, G., Journel, H., Perthus, I., Lespinasse, J., Alessandri, J. -L., Amiel, J., Martinovic, J., Delanne, J., Albuisson, J., Lambert, L., Perrin, L., Ousager, L. B., Van Maldergem, L., Pinson, L., Ruaud, L., Samimi, M., Bournez, M., Bonnet-Dupeyron, M. N., Vincent, M., Jacquemont, M. -L., Cordier-Alex, M. -P., Gerard-Blanluet, M., Willems, M., Spodenkiewicz, M., Doco-Fenzy, M., Rossi, M., Renaud, M., Fradin, M., Mathieu, M., Holder-Espinasse, M. H., Houcinat, N., Hanna, N., Leperrier, N., Chassaing, N., Philip, N., Boute, O., Van Kien, P. K., Parent, P., Bitoun, P., Sarda, P., Vabres, P., Jouk, P. -S., Touraine, R., El Chehadeh, S., Whalen, S., Marlin, S., Passemard, S., Grotto, S., Bellanger, S. A., Blesson, S., Nambot, S., Naudion, S., Lyonnet, S., Odent, S., Attie-Bitach, T., Busa, T., Drouin-Garraud, V., Layet, V., Bizaoui, V., Cusin, V., Capri, Y., Alembik, Y., and Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center]

Subjects
Exome reanalysis, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Multidisciplinaire, généralités & autres [D99] [Sciences de la santé humaine], Developmental disorder, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Biology and Life Sciences, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], ClinVar, Rare diseases, All institutes and research themes of the Radboud University Medical Center, Medicine and Health Sciences, Genetics & genetic processes [F10] [Life sciences], Génétique & processus génétiques [F10] [Sciences du vivant], Multidisciplinary, general & others [D99] [Human health sciences], Exome reanalysi, Genetics (clinical)
Abstract

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion: The "ClinVar low-hanging fruit" analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M. Sí

Published
2023

6. Germline mutations in WNK2 could be associated with serrated polyposis syndrome

Author

Soares de Lima, Y, Arnau-Collell, C, Munoz, J, Herrera-Pariente, C, Moreira, L, Ocana, T, Diaz-Gay, M, Franch-Exposito, S, Cuatrecasas, M, Carballal, S, Lopez-Novo, A, Moreno, L, Fernandez, G, Diaz de Bustamante, A, Peters, S, Sommer, AK, Spier, I, te Paske, IBAW, van Herwaarden, YJ, Castells, A, Bujanda, L, Capella, G, Steinke-Lange, V, Mahmood, K, Joo, JE, Arnold, J, Parry, S, Macrae, FA, Winship, IM, Rosty, C, Cubiella, J, Rodriguez-Alcalde, D, Holinski-Feder, E, de Voer, R, Buchanan, DD, Aretz, S, Ruiz-Ponte, C, Valle, L, Balaguer, F, Bonjoch, L, Castellvi-Bel, S, Soares de Lima, Y, Arnau-Collell, C, Munoz, J, Herrera-Pariente, C, Moreira, L, Ocana, T, Diaz-Gay, M, Franch-Exposito, S, Cuatrecasas, M, Carballal, S, Lopez-Novo, A, Moreno, L, Fernandez, G, Diaz de Bustamante, A, Peters, S, Sommer, AK, Spier, I, te Paske, IBAW, van Herwaarden, YJ, Castells, A, Bujanda, L, Capella, G, Steinke-Lange, V, Mahmood, K, Joo, JE, Arnold, J, Parry, S, Macrae, FA, Winship, IM, Rosty, C, Cubiella, J, Rodriguez-Alcalde, D, Holinski-Feder, E, de Voer, R, Buchanan, DD, Aretz, S, Ruiz-Ponte, C, Valle, L, Balaguer, F, Bonjoch, L, and Castellvi-Bel, S

Abstract

BACKGROUND: Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts. METHODS: After a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. The WNK2 gene was disrupted in HT-29 cells by gene editing, and WNK2 variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion. RESULTS: We identified 2 rare germline variants in the WNK2 gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2. CONCLUSION: After whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in the WNK2 gene. Functional studies suggested germline WNK2 variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease.

Published
2023

9. 1231P Phase I study to evaluate the safety, tolerability, and efficacy of VCN-01 in combination with durvalumab (MEDI4736) in subjects with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC)

Author

Jove, M., primary, Brana, I., additional, Oliva Bernal, M., additional, Hernando-Calvo, A., additional, Erasun Lecuona, C., additional, Assaf Pastrana, J.D., additional, Bazan Peregrino, M., additional, Mato-Berciano, A., additional, Maliandi, M.V., additional, Torres-Manjon, S., additional, Martinez de Villareal, J., additional, Real, F.X., additional, Nuciforo, P.G., additional, Alemany, R., additional, Capella, G., additional, Blasi, E., additional, Blasco, C., additional, Cascallo Piqueras, M., additional, and Mesia Nin, R., additional

Published
2022
Full Text
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11. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Møller, P., Seppälä, T., Dowty, J.G., Haupt, S., Dominguez-Valentin, M., Sunde, L., Bernstein, I., Engel, C., Aretz, S., Nielsen, M., Capella, G., Evans, D.G., Burn, J., Holinski-Feder, E., Bertario, L., Bonanni, B., Lindblom, A., Levi, Z., Macrae, F., Winship, I., Plazzer, J.P., Sijmons, R., Laghi, L., Valle, A.D., Heinimann, K., Half, E., Lopez-Koestner, F., Alvarez-Valenzuela, K., Scott, R.J., Katz, L., Laish, I., Vainer, E., Vaccaro, C.A., Carraro, D.M., Gluck, N., Abu-Freha, N., Stakelum, A., Kennelly, R., Winter, D., Rossi, B.M., Greenblatt, M., Bohorquez, M., Sheth, H., Tibiletti, M.G., Lino-Silva, L.S., Horisberger, K., Portenkirchner, C., Nascimento, I., Rossi, N.T., Silva, L.A. da, Thomas, H, Zaránd, A., Mecklin, J.P., Pylvänäinen, K., Renkonen-Sinisalo, L., Lepisto, A., Peltomäki, P., Therkildsen, C., Lindberg, L.J., Thorlacius-Ussing, O., Doeberitz, M. von Knebel, Loeffler, M., Rahner, N., Steinke-Lange, V., Schmiegel, W., Vangala, D., Perne, C., Hüneburg, R., Vargas, A.F. de, Latchford, A., Gerdes, A.M., Backman, A.S., Guillén-Ponce, C., Snyder, C., Lautrup, C.K., Amor, D., Palmero, E., Stoffel, E., Duijkers, F., Hall, M.J., Hampel, H., Williams, H., Okkels, H., Lubiński, J., Reece, J., Ngeow, J., Guillem, J.G., Arnold, J., Wadt, K., Monahan, K., Senter, L., Rasmussen, L.J., Hest, L.P. van, Ricciardiello, L., Kohonen-Corish, M.R.J., Ligtenberg, M.J.L., Southey, M., Aronson, M., Zahary, M.N., Samadder, N.J., Hoogerbrugge, N., Sampson, J.R., Jenkins, M.A., Møller, P., Seppälä, T., Dowty, J.G., Haupt, S., Dominguez-Valentin, M., Sunde, L., Bernstein, I., Engel, C., Aretz, S., Nielsen, M., Capella, G., Evans, D.G., Burn, J., Holinski-Feder, E., Bertario, L., Bonanni, B., Lindblom, A., Levi, Z., Macrae, F., Winship, I., Plazzer, J.P., Sijmons, R., Laghi, L., Valle, A.D., Heinimann, K., Half, E., Lopez-Koestner, F., Alvarez-Valenzuela, K., Scott, R.J., Katz, L., Laish, I., Vainer, E., Vaccaro, C.A., Carraro, D.M., Gluck, N., Abu-Freha, N., Stakelum, A., Kennelly, R., Winter, D., Rossi, B.M., Greenblatt, M., Bohorquez, M., Sheth, H., Tibiletti, M.G., Lino-Silva, L.S., Horisberger, K., Portenkirchner, C., Nascimento, I., Rossi, N.T., Silva, L.A. da, Thomas, H, Zaránd, A., Mecklin, J.P., Pylvänäinen, K., Renkonen-Sinisalo, L., Lepisto, A., Peltomäki, P., Therkildsen, C., Lindberg, L.J., Thorlacius-Ussing, O., Doeberitz, M. von Knebel, Loeffler, M., Rahner, N., Steinke-Lange, V., Schmiegel, W., Vangala, D., Perne, C., Hüneburg, R., Vargas, A.F. de, Latchford, A., Gerdes, A.M., Backman, A.S., Guillén-Ponce, C., Snyder, C., Lautrup, C.K., Amor, D., Palmero, E., Stoffel, E., Duijkers, F., Hall, M.J., Hampel, H., Williams, H., Okkels, H., Lubiński, J., Reece, J., Ngeow, J., Guillem, J.G., Arnold, J., Wadt, K., Monahan, K., Senter, L., Rasmussen, L.J., Hest, L.P. van, Ricciardiello, L., Kohonen-Corish, M.R.J., Ligtenberg, M.J.L., Southey, M., Aronson, M., Zahary, M.N., Samadder, N.J., Hoogerbrugge, N., Sampson, J.R., and Jenkins, M.A.

Abstract

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Published
2022

12. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Moller, P, Seppala, T, Dowty, JG, Haupt, S, Dominguez-Valentin, M, Sunde, L, Bernstein, I, Engel, C, Aretz, S, Nielsen, M, Capella, G, Evans, DG, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J-P, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Half, E, Lopez-Koestner, F, Alvarez-Valenzuela, K, Scott, RJ, Katz, L, Laish, I, Vainer, E, Vaccaro, CA, Carraro, DM, Gluck, N, Abu-Freha, N, Stakelum, A, Kennelly, R, Winter, D, Rossi, BM, Greenblatt, M, Bohorquez, M, Sheth, H, Tibiletti, MG, Lino-Silva, LS, Horisberger, K, Portenkirchner, C, Nascimento, I, Rossi, NT, da Silva, LA, Thomas, H, Zarand, A, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Therkildsen, C, Lindberg, LJ, Thorlacius-Ussing, O, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hueneburg, R, de Vargas, AF, Latchford, A, Gerdes, A-M, Backman, A-S, Guillen-Ponce, C, Snyder, C, Lautrup, CK, Amor, D, Palmero, E, Stoffel, E, Duijkers, F, Hall, MJ, Hampel, H, Williams, H, Okkels, H, Lubinski, J, Reece, J, Ngeow, J, Guillem, JG, Arnold, J, Wadt, K, Monahan, K, Senter, L, Rasmussen, LJ, van Hest, LP, Ricciardiello, L, Kohonen-Corish, MRJ, Ligtenberg, MJL, Southey, M, Aronson, M, Zahary, MN, Samadder, NJ, Poplawski, N, Hoogerbrugge, N, Morrison, PJ, James, P, Lee, G, Chen-Shtoyerman, R, Ankathil, R, Pai, R, Ward, R, Parry, S, Debniak, T, John, T, van Overeem Hansen, T, Caldes, T, Yamaguchi, T, Barca-Tierno, V, Garre, P, Cavestro, GM, Weitz, J, Redler, S, Buettner, R, Heuveline, V, Hopper, JL, Win, AK, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, J, Buchanan, DD, Thibodeau, SN, ten Broeke, SW, Hovig, E, Nakken, S, Pineda, M, Duenas, N, Brunet, J, Green, K, Lalloo, F, Newton, K, Crosbie, EJ, Mints, M, Tjandra, D, Neffa, F, Esperon, P, Kariv, R, Rosner, G, Pavicic, WH, Kalfayan, P, Torrezan, GT, Bassaneze, T, Martin, C, Moslein, G, Ahadova, A, Kloor, M, Sampson, JR, Jenkins, MA, Moller, P, Seppala, T, Dowty, JG, Haupt, S, Dominguez-Valentin, M, Sunde, L, Bernstein, I, Engel, C, Aretz, S, Nielsen, M, Capella, G, Evans, DG, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J-P, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Half, E, Lopez-Koestner, F, Alvarez-Valenzuela, K, Scott, RJ, Katz, L, Laish, I, Vainer, E, Vaccaro, CA, Carraro, DM, Gluck, N, Abu-Freha, N, Stakelum, A, Kennelly, R, Winter, D, Rossi, BM, Greenblatt, M, Bohorquez, M, Sheth, H, Tibiletti, MG, Lino-Silva, LS, Horisberger, K, Portenkirchner, C, Nascimento, I, Rossi, NT, da Silva, LA, Thomas, H, Zarand, A, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Therkildsen, C, Lindberg, LJ, Thorlacius-Ussing, O, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hueneburg, R, de Vargas, AF, Latchford, A, Gerdes, A-M, Backman, A-S, Guillen-Ponce, C, Snyder, C, Lautrup, CK, Amor, D, Palmero, E, Stoffel, E, Duijkers, F, Hall, MJ, Hampel, H, Williams, H, Okkels, H, Lubinski, J, Reece, J, Ngeow, J, Guillem, JG, Arnold, J, Wadt, K, Monahan, K, Senter, L, Rasmussen, LJ, van Hest, LP, Ricciardiello, L, Kohonen-Corish, MRJ, Ligtenberg, MJL, Southey, M, Aronson, M, Zahary, MN, Samadder, NJ, Poplawski, N, Hoogerbrugge, N, Morrison, PJ, James, P, Lee, G, Chen-Shtoyerman, R, Ankathil, R, Pai, R, Ward, R, Parry, S, Debniak, T, John, T, van Overeem Hansen, T, Caldes, T, Yamaguchi, T, Barca-Tierno, V, Garre, P, Cavestro, GM, Weitz, J, Redler, S, Buettner, R, Heuveline, V, Hopper, JL, Win, AK, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, J, Buchanan, DD, Thibodeau, SN, ten Broeke, SW, Hovig, E, Nakken, S, Pineda, M, Duenas, N, Brunet, J, Green, K, Lalloo, F, Newton, K, Crosbie, EJ, Mints, M, Tjandra, D, Neffa, F, Esperon, P, Kariv, R, Rosner, G, Pavicic, WH, Kalfayan, P, Torrezan, GT, Bassaneze, T, Martin, C, Moslein, G, Ahadova, A, Kloor, M, Sampson, JR, and Jenkins, MA

Abstract

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Published
2022

13. Correction: Solving unsolved rare neurological diseases—a Solve-RD viewpoint (European Journal of Human Genetics, (2021), 29, 9, (1332-1336), 10.1038/s41431-021-00901-1)

Author

Schule R., Timmann D., Erasmus C. E., Reichbauer J., Wayand M., Baets J., Balicza P., Chinnery P., Durr A., Haack T., Hengel H., Horvath R., Houlden H., Kamsteeg E. -J., Kamsteeg C., Lohmann K., Macaya A., Marce-Grau A., Maver A., Molnar J., Munchau A., Peterlin B., Riess O., Schols L., Stevanin G., Synofzik M., Timmerman V., van de Warrenburg B., van Os N., Vandrovcova J., Wilke C., Bevot A., Zuchner S., Beltran S., Laurie S., Matalonga L., Graessner H., Zurek B., Ellwanger K., Ossowski S., Demidov G., Sturm M., Schulze-Hentrich J. M., Heutink P., Brunner H., Scheffer H., Hoogerbrugge N., Hoischen A., 't Hoen P. A. C., Vissers L. E. L. M., Gilissen C., Steyaert W., Sablauskas K., de Voer R. M., Janssen E., de Boer E., Steehouwer M., Yaldiz B., Kleefstra T., Brookes A. J., Veal C., Gibson S., Wadsley M., Mehtarizadeh M., Riaz U., Warren G., Dizjikan F. Y., Shorter T., Topf A., Straub V., Bettolo C. M., Specht S., Clayton-Smith J., Banka S., Alexander E., Jackson A., Faivre L., Thauvin C., Vitobello A., Denomme-Pichon A. -S., Duffourd Y., Tisserant E., Bruel A. -L., Peyron C., Pelissier A., Gut I. G., Piscia D., Papakonstantinou A., Bullich G., Corvo A., Garcia C., Fernandez-Callejo M., Hernandez C., Pico D., Paramonov I., Lochmuller H., Gumus G., Bros-Facer V., Rath A., Hanauer M., Olry A., Lagorce D., Havrylenko S., Izem K., Rigour F., Davoine C. -S., Guillot-Noel L., Heinzmann A., Coarelli G., Bonne G., Evangelista T., Allamand V., Nelson I., Yaou R. B., Metay C., Eymard B., Cohen E., Atalaia A., Stojkovic T., Macek M., Turnovec M., Thomasova D., Kremlikova R. P., Frankova V., Havlovicova M., Kremlik V., Parkinson H., Keane T., Spalding D., Senf A., Robinson P., Danis D., Robert G., Costa A., Patch C., Hanna M., Reilly M., Muntoni F., Zaharieva I., Sarkozy A., de Jonghe P., Nigro V., Banfi S., Torella A., Musacchia F., Piluso G., Ferlini A., Selvatici R., Rossi R., Neri M., Aretz S., Spier I., Sommer A. K., Peters S., Oliveira C., Pelaez J. G., Matos A. R., Jose C. S., Ferreira M., Gullo I., Fernandes S., Garrido L., Ferreira P., Carneiro F., Swertz M. A., Johansson L., van der Velde J. K., van der Vries G., Neerincx P. B., Roelofs-Prins D., Kohler S., Metcalfe A., Verloes A., Drunat S., Rooryck C., Trimouille A., Castello R., Morleo M., Pinelli M., Varavallo A., De la Paz M. P., Sanchez E. B., Martin E. L., Delgado B. M., de la Rosa F. J. A. G., Ciolfi A., Dallapiccola B., Pizzi S., Radio F. C., Tartaglia M., Renieri A., Benetti E., Molnar M. J., Herzog R., Pauly M., Osorio A. N., de Benito D. N., Thompson R., Polavarapu K., Beeson D., Cossins J., Cruz P. M. R., Hackman P., Johari M., Savarese M., Udd B., Capella G., Valle L., Holinski-Feder E., Laner A., Steinke-Lange V., Schrock E., Rump A., Schule, R., Timmann, D., Erasmus, C. E., Reichbauer, J., Wayand, M., Baets, J., Balicza, P., Chinnery, P., Durr, A., Haack, T., Hengel, H., Horvath, R., Houlden, H., Kamsteeg, E. -J., Kamsteeg, C., Lohmann, K., Macaya, A., Marce-Grau, A., Maver, A., Molnar, J., Munchau, A., Peterlin, B., Riess, O., Schols, L., Stevanin, G., Synofzik, M., Timmerman, V., van de Warrenburg, B., van Os, N., Vandrovcova, J., Wilke, C., Bevot, A., Zuchner, S., Beltran, S., Laurie, S., Matalonga, L., Graessner, H., Zurek, B., Ellwanger, K., Ossowski, S., Demidov, G., Sturm, M., Schulze-Hentrich, J. M., Heutink, P., Brunner, H., Scheffer, H., Hoogerbrugge, N., Hoischen, A., 't Hoen, P. A. C., Vissers, L. E. L. M., Gilissen, C., Steyaert, W., Sablauskas, K., de Voer, R. M., Janssen, E., de Boer, E., Steehouwer, M., Yaldiz, B., Kleefstra, T., Brookes, A. J., Veal, C., Gibson, S., Wadsley, M., Mehtarizadeh, M., Riaz, U., Warren, G., Dizjikan, F. Y., Shorter, T., Topf, A., Straub, V., Bettolo, C. M., Specht, S., Clayton-Smith, J., Banka, S., Alexander, E., Jackson, A., Faivre, L., Thauvin, C., Vitobello, A., Denomme-Pichon, A. -S., Duffourd, Y., Tisserant, E., Bruel, A. -L., Peyron, C., Pelissier, A., Gut, I. G., Piscia, D., Papakonstantinou, A., Bullich, G., Corvo, A., Garcia, C., Fernandez-Callejo, M., Hernandez, C., Pico, D., Paramonov, I., Lochmuller, H., Gumus, G., Bros-Facer, V., Rath, A., Hanauer, M., Olry, A., Lagorce, D., Havrylenko, S., Izem, K., Rigour, F., Davoine, C. -S., Guillot-Noel, L., Heinzmann, A., Coarelli, G., Bonne, G., Evangelista, T., Allamand, V., Nelson, I., Yaou, R. B., Metay, C., Eymard, B., Cohen, E., Atalaia, A., Stojkovic, T., Macek, M., Turnovec, M., Thomasova, D., Kremlikova, R. P., Frankova, V., Havlovicova, M., Kremlik, V., Parkinson, H., Keane, T., Spalding, D., Senf, A., Robinson, P., Danis, D., Robert, G., Costa, A., Patch, C., Hanna, M., Reilly, M., Muntoni, F., Zaharieva, I., Sarkozy, A., de Jonghe, P., Nigro, V., Banfi, S., Torella, A., Musacchia, F., Piluso, G., Ferlini, A., Selvatici, R., Rossi, R., Neri, M., Aretz, S., Spier, I., Sommer, A. K., Peters, S., Oliveira, C., Pelaez, J. G., Matos, A. R., Jose, C. S., Ferreira, M., Gullo, I., Fernandes, S., Garrido, L., Ferreira, P., Carneiro, F., Swertz, M. A., Johansson, L., van der Velde, J. K., van der Vries, G., Neerincx, P. B., Roelofs-Prins, D., Kohler, S., Metcalfe, A., Verloes, A., Drunat, S., Rooryck, C., Trimouille, A., Castello, R., Morleo, M., Pinelli, M., Varavallo, A., De la Paz, M. P., Sanchez, E. B., Martin, E. L., Delgado, B. M., de la Rosa, F. J. A. G., Ciolfi, A., Dallapiccola, B., Pizzi, S., Radio, F. C., Tartaglia, M., Renieri, A., Benetti, E., Molnar, M. J., Herzog, R., Pauly, M., Osorio, A. N., de Benito, D. N., Thompson, R., Polavarapu, K., Beeson, D., Cossins, J., Cruz, P. M. R., Hackman, P., Johari, M., Savarese, M., Udd, B., Capella, G., Valle, L., Holinski-Feder, E., Laner, A., Steinke-Lange, V., Schrock, E., and Rump, A.

Abstract

In the original publication of the article, consortium author lists were missing in the article. The details are given below

Published
2021

16. Genetic Alterations

Author

Perucho, M., Schaeffer, J., Velazquez, A., Berrozpe, G., Capella, G., Pederzoli, Paolo, editor, Cavallini, Giorgio, editor, Bassi, Claudio, editor, and Falconi, Massimo, editor

Published
1994
Full Text
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17. A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report

Author

te Paske, I.B.A.W., Garcia-Pelaez, J., Sommer, A.K., Matalonga, L., Starzynska, T., Jakubowska, A., Valle, L., Capella, G., Aretz, S., Holinski-Feder, E., Steinke-Lange, V., Laner, A., Schröck, E., Rump, A., Ligtenberg, M., Hoischen, A., Geverink, N., Evans, D.G., Tischkowitz, M., Laurie, S., van der Post, R.S., Lubinski, J., Oliveira, C., Hoogerbrugge, N., de Voer, R.M., Sommer, Anna K [0000-0001-6850-9290], Starzynska, Teresa [0000-0001-5573-2397], Jakubowska, Anna [0000-0002-5650-0501], Hoogerbrugge, Nicoline [0000-0003-2393-8141], de Voer, Richarda M [0000-0002-8222-0343], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Adult, Somatic cell, Class I Phosphatidylinositol 3-Kinases, Mutation, Missense, Stomach Neoplasms/genetics, Brief Communication, Whole Exome Sequencing, Germline, CDH1, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Exome Sequencing, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Genetics, medicine, Cancer genomics, Missense mutation, Humans, Young adult, Genetics (clinical), Class I Phosphatidylinositol 3-Kinases/genetics, biology, business.industry, Mosaicism, Cancer, medicine.disease, Phenotype, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Female, Hereditary diffuse gastric cancer, business, Gastric cancer
Abstract

Hereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257. The research work at i3S/Ipatimup is supported by the European Regional Development Fund (ERDF) through COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and Project Ref. POCI-01-0145-FEDER-030164. Data was reanalysed using the RD‐Connect Genome‐Phenome Analysis Platform, which received funding from EU projects RD‐Connect, Solve-RD and EJP-RD (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática, INB) and ELIXIR Implementation Studies.

Published
2021

18. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (Genetics in Medicine, (2020), 22, 1, (15-25), 10.1038/s41436-019-0596-9)

Author

Dominguez-Valentin M., Sampson J. R., Seppala T. T., ten Broeke S. W., Plazzer J. -P., Nakken S., Engel C., Aretz S., Jenkins M. A., Sunde L., Bernstein I., Capella G., Balaguer F., Thomas H., Evans D. G., Burn J., Greenblatt M., Hovig E., de Vos tot Nederveen Cappel W. H., Sijmons R. H., Bertario L., Tibiletti M. G., Cavestro G. M., Lindblom A., Della Valle A., Lopez-Kostner F., Gluck N., Katz L. H., Heinimann K., Vaccaro C. A., Buttner R., Gorgens H., Holinski-Feder E., Morak M., Holzapfel S., Huneburg R., Knebel Doeberitz M., Loeffler M., Rahner N., Schackert H. K., Steinke-Lange V., Schmiegel W., Vangala D., Pylvanainen K., Renkonen-Sinisalo L., Hopper J. L., Win A. K., Haile R. W., Lindor N. M., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J. C., Thibodeau S. N., Wadt K., Therkildsen C., Okkels H., Ketabi Z., Moreira L., Sanchez A., Serra-Burriel M., Pineda M., Navarro M., Blanco I., Green K., Lalloo F., Crosbie E. J., Hill J., Denton O. G., Frayling I. M., Rodland E. A., Vasen H., Mints M., Neffa F., Esperon P., Alvarez K., Kariv R., Rosner G., Pinero T. A., Gonzalez M. L., Kalfayan P., Tjandra D., Winship I. M., Macrae F., Moslein G., Mecklin J. -P., Nielsen M., Moller P., Dominguez-Valentin, M., Sampson, J. R., Seppala, T. T., ten Broeke, S. W., Plazzer, J. -P., Nakken, S., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., Hovig, E., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Bertario, L., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Della Valle, A., Lopez-Kostner, F., Gluck, N., Katz, L. H., Heinimann, K., Vaccaro, C. A., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., Knebel Doeberitz, M., Loeffler, M., Rahner, N., Schackert, H. K., Steinke-Lange, V., Schmiegel, W., Vangala, D., Pylvanainen, K., Renkonen-Sinisalo, L., Hopper, J. L., Win, A. K., Haile, R. W., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Wadt, K., Therkildsen, C., Okkels, H., Ketabi, Z., Moreira, L., Sanchez, A., Serra-Burriel, M., Pineda, M., Navarro, M., Blanco, I., Green, K., Lalloo, F., Crosbie, E. J., Hill, J., Denton, O. G., Frayling, I. M., Rodland, E. A., Vasen, H., Mints, M., Neffa, F., Esperon, P., Alvarez, K., Kariv, R., Rosner, G., Pinero, T. A., Gonzalez, M. L., Kalfayan, P., Tjandra, D., Winship, I. M., Macrae, F., Moslein, G., Mecklin, J. -P., Nielsen, M., and Moller, P.

Abstract

The original version of this Article did not contain details of Dutch Cancer Society (DCS) funding (grant number UL 2017-8223) in the Acknowledgements section. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2020

19. First international workshop of the ATM and Cancer Risk Group (4–5 December 2019)

Author

Lesueur, F., Easton, D. F., Renault, A. -L., Tavtigian, S. V., Bernstein, J. L., Kote-Jarai, Z., Eeles, R. A., Plaseska-Karanfia, D., Feliubadalo, L., Moles-Fernandez, A., Santamarina-Pena, M., Sanchez, A. T., Lopez-Novo, A., Porras, L. -M., Blanco, A., Capella, G., de la Hoya, M., Molina, I. J., Osorio, A., Pineda, M., Rueda, D., de la Cruz, X., Diez, O., Ruiz-Ponte, C., Gutierrez-Enriquez, S., Vega, A., Lazaro, C., Arun, B., Herold, N., Versmold, B., Schmutzler, R. K., Nguyen-Dumont, T., Southey, M. C., Dorling, L., Dunning, A. M., Ghiorzo, P., Dalmasso, B. S., Cavaciuti, E., Le Gal, D., Roberts, N. J., Dominguez-Valentin, M., Rookus, M., Taylor, A. M. R., Goldstein, A. M., Goldgar, D. E., Couch, F., Kraft, P., Weitzel, J., Nathanson, K., Domchek, S., Laduca, H., Stoppa-Lyonnet, D., and Andrieu, N.

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Heterozygote, Variants classification, ATM, Cancer risk, Cancer spectrum, Tumor profiles, Population, Context (language use), Breast Neoplasms, Ataxia Telangiectasia Mutated Proteins, 030105 genetics & heredity, Article, 03 medical and health sciences, Ataxia Telangiectasia, 0302 clinical medicine, Neoplasms, Epidemiology, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Genetics (clinical), education.field_of_study, business.industry, Cancer, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Family medicine, Female, France, business
Abstract

The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to ATM and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for ATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that ATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary.

Published
2021

20. Latent tuberculosis infection in patients with chronic plaque psoriasis: evidence from the Italian Psocare Registry*

Author

Gisondi, P., Cazzaniga, S., Chimenti, S., Maccarone, M., Picardo, M., Girolomoni, G., Naldi, L., Griseta, V., Miracapillo, A., Azzini, M., Mocci, L., Michelini, M., Offidani, A., Bernardini, L., Campanati, A., Ricotti, G., Giacchetti, A., Norat, M., Gualco, F., Castelli, A., Cuccia, A., Diana, A., Roncarolo, G., Belli, M. A., Baldassarre, M. A., Santoro, G., Vena, G. A., Lo Console, F., Filotico, R., Mastrandrea, V., Brunetti, B., Musumeci, F., Carrabba, E., Dal Mas, P., Annicchiarico, F., Benvegnù, B., Spaziani, G., Cusano, F., Iannazzone, Saletta S., Galluccio, A., Pezza, M., Marchesi, L., Imberti, G., Reseghetti, A., Barbera, C., Reggiani, M., Lanzoni, A., Patrizi, A., Bardazzi, F., Antonucci, A., De Tommaso, S., Balestri, R., Wallnofer, W., Ingannamorte, F., Calzavara-Pinton, P., Iannazzi, S., Zane, C., Capezzera, R., Bassisi, S., Rossi, M. T., Altamura, V., Vigl, W., Nobile, C., Aste, N., Murgia, S., Mugheddu, C., Scuderi, G., Baglieri, F., Di Dio, C., Grilli, Cilioni E., Mastronardi, C., Agnusdei, C. P., Antrilli, A., Aulisa, L., Raimondo, U., di Luzio, Scotto G., Battarra, V. C., Farro, P., Plaitano, R., Micali, G., Musumeci, M. L., Massimino, D., Li Calzi, M., La Greca, S., Pettinato, M., Sapienza, G., Valenti, G., De Giacomo, P. F., dʼAmico, D., Arcangeli, F., Brunelli, D., Ghetti, E., Tulli, A., Assi, G., Laria, G., Prestinari, F., Spadafora, S., Coppola, M., Caresana, G., Pezzarossa, E., Domaneschi, E., Felisi, C., Donato, L., Bertero, M., Musso, L., Pa lazzini, S., Bruscino, P., Agozzino, U. C., Ottaviani, M., Simoncini, C., Virgili, A., Osti, F., Fabbri, P., Volpi, W., Caproni, M., Lotti, T., Prignano, F., Buggiani, G., Troiano, M., Fenizi, G., Altobella, A., Amoruso, A., Condello, M., Goffredo, A., Righini, M. G., Alessandrini, F., Satolli, F., Zampetti, M., Bertani, E., Fossati, S., Parodi, A., Burlando, M., Fiorucci, C., Nigro, A., Ghigliotti, G., Massone, L., Moise, G. M., Serrai, M., Cannata, G., Campagnoli, A. M., Daly, M., Leporati, C., Peila, R., Filosa, G., Bugatti, L., Nicolini, M., Nazzari, G., Cestari, R., Anastasio, F., Larussa, F. M., Pollice, N., De Francesco, F., Mazzocchetti, G., Peris, K., Fargnoli, M. C., Di Cesare, A., De Angelis, L., Flati, G., Biamonte, A. S., Quarta, G., Congedo, M., Carcaterra, A., Strippoli, D., Fideli, D., Marsili, F., Celli, M., Ceccarini, M., Bachini, L., DʼOria, M., Schirripa, V., De Filippi, C., Martini, P., Lapucci, E., Mazzatenta, C., Ghilardi, A., Simonacci, M., Bettacchi, A., Gasco, R., Zanca, A., Battistini, S., Dattola, S., Vernaci, R., Postorino, F., Zampieri, P. F., Padovan, C., González Intchaurraga, M. A., Ladurner, J., Guarneri, B., Cannavò, S., Manfrè, C., Borgia, F., Guerra, Puglisi A., Sedona, P., Cattaneo, A., Carrera, C., Fracchiolla, C., Mozzanica, N., Prezzemolo, L., Menni, S., Lodi, A., Martino, P., Monti, M., Mancini, L., Sacrini, F., Altomare, G. F., Taglioni, M., Lovati, C., Mercuri, S. R., Schiesari, G., Giannetti, A., Conti, A., Lasagni, C., Greco, M., Ronsini, G., Schianchi, S., Fiorentini, C., Niglietta, S., Maglietta, R., Padalino, C., Crippa, D., Pini, M., Rossi, E., Tosi, D., Armas, M., Ruocco, V., Ayala, F., Balato, N., Gaudiello, F., Cimmino, G. F., Monfrecola, G., Gallo, L., Argenziano, G., Fulgione, E., Berruti, G., Mozzillo, R., Ceparano, S., De Michele, I., Giorgiano, D., Leigheb, G., Deledda, S., Peserico, A., Alaibac, M., Piaserico, S., Schiesari, L., Dan, G., Mattei, I., Oro, E., Aricò, M., Bongiorno, M. R., Angileri, R., Amato, S., Todaro, F., Milioto, M., Bellastro, R., Di Nuzzo, S., De Panfilis, G., Zanni, M., Borroni, G., Cananzi, R., Brazzelli, V., Lisi, P., Stingeni, L., Hansel, K., Pierfelice, V., Donelli, S., Rastelli, D., Gasperini, M., Barachini, P., Cecchi, R., Bartoli, L., Pavesi, M., De Paola, S., Corradin, M. T., Ricciuti, F., Piccirillo, A., Viola, L., Tataranni, M., Mautone, M. G., Lo Scocco, G., Niccoli, M. C., Brunasso Vernetti, A. M.G., Gaddoni, G., Resta, F., Casadio, M. C., Arcidiaco, M. C., Luvarà, M. C., Albertini, G., Di Lernia, V., Guareschi, E., Catrani, S., Morri, M., Amerio, P., De Simone, C., DʼAgostino, M., Agostino, I., Calvieri, S., Cantoresi, F., Richetta, A., Sorgi, P., Carnevale, C., Nicolucci, F., Berardesca, E., Ardigò, M., De Felice, C., Gubinelli, E., Talamonti, M., Camplone, G., Cruciani, G., Riccardi, F., Barbati, R., Pagani, W., Malagoli, P. G., Pellicano, R., Donadio, D., Di Vito, C., Cottoni, F., Montesu, M. A., Pirodda, C., Addis, G., Marongiu, P., Farris, A., Cacciapuoti, M., Verrini, A., Desirello, G., Gnone, M., Fimiani, M., Pellegrino, M., Castelli, G., Zappalà, L., Sesana, G., Ingordo, V., Vozza, E., Di Giuseppe, D., Fasciocco, D., Nespoli, P., Papini, M., Cicoletti, M., Bernengo, M. G., Ortoncelli, M., Bonvicino, A., Capella, G., Doveil, G. C., Forte, M., Peroni, A., Salomone, B., Savoia, P., Pippione, M., Zichichi, L., Frazzitta, M., De Luca, G., Tasin, L., Simonetto, D., Ros, S., Trevisan, G., Patamia, M., Miertusova, S., Patrone, P., Frattasio, A., Piccirillo, F., La Spina, S., Di Gaetano, L., Marzocchi, V., Motolese, A., Venturi, C., Gai, F., Pasquinucci, S., Bellazzi, R. M., Silvestri, T., Fornasa, Veller C., and Trevisan, G. P.

Published
2015
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21. Characteristics of Adrenocortical Carcinoma Associated With Lynch Syndrome

Author

Domenech, M, Grau, E, Solanes, A, Izquierdo, A, Del Valle, J, Carrato, C, Pineda, M, Duenas, N, Pujol, M, Lazaro, C, Capella, G, Brunet, J, and Navarro, M

Subjects
Lynch syndrome, adrenocortical carcinoma, molecular characteristics
Abstract

Context Lynch syndrome (LS) is the most common inherited colorectal and endometrial cancer syndrome, caused by germline mutations in DNA mismatch repair (MMR) genes. It is also characterized by an increased risk of other tumors with lower prevalence, such as adrenal cortical carcinoma (ACC), an endocrine tumor with an incidence of

Published
2021

22. GENOTYPE-PHENOTYPE ASSOCIATIONS PROVIDE A RATIONAL TO IDENTIFY POTENTIALLY ACTIONABLE VUS

Author

Pelaez J, Monteiro R, Lobo S, Sousa L, Pinheiro H, Castedo S, Garrido L, Teixeira M, Michils G, Bours V, de Putter R, Golmard L, Blanluet M, Colas C, Benusiglio P, Desseignes C, Florence C, Aretz S, Spier I, Huneburg R, Gieldon L, Schrock E, Holinski-Feder E, Steinke V, Calistri D, Tedaldi G, Ranzani G, Genuardi M, Silveira C, Silva I, Krajc M, Blatnik A, Novacovik S, Patino-Garcia A, Soto J, Lazaro C, Capella G, Brunet-Vidal J, Balmana J, Dominguez-Garrido E, Ligtenberg M, Fewings E, Fitzgerald R, Woodward E, Evans G, Hanson H, Lagerstedt-Robinson K, Bajalica-Lagercrantz S, Egas C, Tejada M, Dahan K, Feret D, Hoogerbrugge N, Tischkowitz M, and Oliveira C

Published
2021

23. First international workshop of the ATM and cancer risk group (4-5 December 2019).

Author

Lesueur F., Easton D.F., Renault A.-L., Tavtigian S.V., Bernstein J.L., Kote-Jarai Z., Eeles R.A., Plaseska-Karanfia D., Feliubadalo L., Moles-Fernandez A., Santamarina-Pena M., Sanchez A.T., Lopez-Novo A., Porras L.-M., Blanco A., Capella G., de la Hoya M., Molina I.J., Osorio A., Pineda M., Rueda D., de la Cruz X., Diez O., Ruiz-Ponte C., Gutierrez-Enriquez S., Vega A., Lazaro C., Arun B., Herold N., Versmold B., Schmutzler R.K., Nguyen-Dumont T., Southey M.C., Dorling L., Dunning A.M., Ghiorzo P., Dalmasso B.S., Cavaciuti E., Le Gal D., Roberts N.J., Dominguez-Valentin M., Rookus M., Taylor A.M.R., Goldstein A.M., Goldgar D.E., Couch F., Kraft P., Weitzel J., Nathanson K., Domchek S., LaDuca H., Stoppa-Lyonnet D., Andrieu N., Lesueur F., Easton D.F., Renault A.-L., Tavtigian S.V., Bernstein J.L., Kote-Jarai Z., Eeles R.A., Plaseska-Karanfia D., Feliubadalo L., Moles-Fernandez A., Santamarina-Pena M., Sanchez A.T., Lopez-Novo A., Porras L.-M., Blanco A., Capella G., de la Hoya M., Molina I.J., Osorio A., Pineda M., Rueda D., de la Cruz X., Diez O., Ruiz-Ponte C., Gutierrez-Enriquez S., Vega A., Lazaro C., Arun B., Herold N., Versmold B., Schmutzler R.K., Nguyen-Dumont T., Southey M.C., Dorling L., Dunning A.M., Ghiorzo P., Dalmasso B.S., Cavaciuti E., Le Gal D., Roberts N.J., Dominguez-Valentin M., Rookus M., Taylor A.M.R., Goldstein A.M., Goldgar D.E., Couch F., Kraft P., Weitzel J., Nathanson K., Domchek S., LaDuca H., Stoppa-Lyonnet D., and Andrieu N.

Abstract

The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the clinical utility of ATM variant testing is uncertain. The meeting brought together epidemiologists, geneticists, biologists and clinicians to review current knowledge and on-going challenges related to ATM and cancer risk. This report summarizes the meeting sessions content that covered the latest results in family-based and population-based studies, the importance of accurate variant classification, the effect of radiation exposures for ATM variant carriers, and the characteristics of ATM-deficient tumors. The report concludes that ATM variant carriers outside of the context of Ataxia-Telangiectasia may benefit from effective cancer risk management and therapeutic strategies and that efforts to set up large-scale studies in the international framework to achieve this goal are necessary.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Published
2021

24. The 'unnatural' history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance

Author

Ahadova, A, Seppala, TT, Engel, C, Gallon, R, Burn, J, Holinski-Feder, E, Steinke-Lange, V, Moeslein, G, Nielsen, M, ten Broeke, SW, Laghi, L, Dominguez-Valentin, M, Capella, G, Macrae, F, Scott, R, Hueneburg, R, Nattermann, J, Hoffmeister, M, Brenner, H, Blaeker, H, Doeberitz, MVK, Sampson, JR, Vasen, H, Mecklin, J-P, Moller, P, Kloor, M, Ahadova, A, Seppala, TT, Engel, C, Gallon, R, Burn, J, Holinski-Feder, E, Steinke-Lange, V, Moeslein, G, Nielsen, M, ten Broeke, SW, Laghi, L, Dominguez-Valentin, M, Capella, G, Macrae, F, Scott, R, Hueneburg, R, Nattermann, J, Hoffmeister, M, Brenner, H, Blaeker, H, Doeberitz, MVK, Sampson, JR, Vasen, H, Mecklin, J-P, Moller, P, and Kloor, M

Abstract

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.

Published
2021

25. Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Author

Seppala, TT, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Vida, JB, Kariv, R, Rosner, G, Pinero, TA, Pavicic, W, Kalfayan, P, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Redler, S, Weitz, J, Pylvaenaeinen, K, Renkonen-Sinisalo, L, Lepisto, A, Hopper, JL, Win, AK, Lindor, NM, Gallinger, S, Marchand, LL, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Wadt, KAW, Mourits, MJE, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Rokkones, E, Sampson, JR, Evans, DG, Moller, P, Seppala, TT, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Vida, JB, Kariv, R, Rosner, G, Pinero, TA, Pavicic, W, Kalfayan, P, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Redler, S, Weitz, J, Pylvaenaeinen, K, Renkonen-Sinisalo, L, Lepisto, A, Hopper, JL, Win, AK, Lindor, NM, Gallinger, S, Marchand, LL, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Wadt, KAW, Mourits, MJE, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Rokkones, E, Sampson, JR, Evans, DG, and Moller, P

Abstract

PURPOSE: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years. RESULTS: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. CONCLUSION: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes.

Published
2021

26. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Author

Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Nakken, S, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Brunet Vidal, J, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Ryan, N, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Auranen, A, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Okkels, H, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Sampson, JR, Evans, DG, Seppala, TT, Moller, P, Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Nakken, S, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Brunet Vidal, J, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Ryan, N, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Auranen, A, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Okkels, H, Ketabi, Z, Denton, OG, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Sampson, JR, Evans, DG, Seppala, TT, and Moller, P

Abstract

PURPOSE: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. RESULTS: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. CONCLUSION: Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

Published
2021

27. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study

Author

Dominguez-Valentin, M, Plazzer, J-P, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Cappel, WHDVTN, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sanchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Pinero, TA, Pavicic, WH, Kalfayan, P, ten Broeke, SW, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Hansen, TVO, Lindberg, L, Rodland, EA, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Seppala, TT, Moller, P, Dominguez-Valentin, M, Plazzer, J-P, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Cappel, WHDVTN, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sanchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Pinero, TA, Pavicic, WH, Kalfayan, P, ten Broeke, SW, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Hansen, TVO, Lindberg, L, Rodland, EA, Neffa, F, Esperon, P, Tjandra, D, Moslein, G, Seppala, TT, and Moller, P

Abstract

BACKGROUND: 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. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. OBJECTIVE: To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. METHODS: Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. RESULTS: Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. CONCLUSION: Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

Published
2021

28. 937P Survival outcomes in phase I trial combining VCN-01 and durvalumab (MEDI4736) in subjects with recurrent/metastatic head and neck squamous cell carcinoma refractory to previous immunotherapy treatment

Author

Jové, M., Braña, I., Oliva Bernal, M., Hernando Calvo, A., Erasun Lecuona, C., Assaf Pastrana, J.D., Mato-Berciano, A., Maliandi, M.V., Torres-Manjon, S., Moreno, R., Le, C., Nuciforo, P.G., Alemany, R., Capella, G., Blasco, C., Cascallo Piqueras, M., and Mesia Nin, R.

Published
2023
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29. Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST)

Author

Crusius, J.B.A., Canzian, F., Capellá, G., Peña, A.S., Pera, G., Sala, N., Agudo, A., Rico, F., Del Giudice, G., Palli, D., Plebani, M., Boeing, H., Bueno-de-Mesquita, H.B., Carneiro, F., Pala, V., Save, V.E., Vineis, P., Tumino, R., Panico, S., Berglund, G., Manjer, J., Stenling, R., Hallmans, G., Martínez, C., Dorronsoro, M., Barricarte, A., Navarro, C., Quirós, J.R., Allen, N., Key, T.J., Binghan, S., Caldas, C., Linseisen, J., Kaaks, R., Overvad, K., Tjønneland, A., Büchner, F.C., Peeters, P.H.M., Numans, M.E., Clavel-Chapelon, F., Trichopoulou, A., Lund, E., Jenab, M., Rinaldi, S., Ferrari, P., Riboli, E., and González, C.A.

Published
2008
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30. Recommendations to improve identification of hereditary and familial colorectal cancer in Europe

Author

Vasen, H. F. A., Möslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Rahner, N., Hes, F. J., Hodgson, S., Mecklin, J.-P., Møller, P., Myrhøj, T., Nagengast, F. M., Parc, Y., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J. R., Stormorken, A., Tejpar, S., Thomas, H. J. W., Wijnen, J., Lubinski, J., Järvinen, H., Claes, E., Heinimann, K., Karagiannis, J. A., Lindblom, A., Dove-Edwin, I., and Müller, H.

Published
2010
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31. Peutz-Jeghers syndrome: a systematic review and recommendations for management

Author

Beggs, A.D., Latchford, A.R., Vasen, H.F.A., Moslein, G., Alonso, A., Aretz, S., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Friedl, W., Moller, P., Hes, F.J., Jarvinen, H., Mecklin, J.-P., Nagengast, F.M., Parc, Y., Phillips, R.K.S., Hyer, W., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J.W., Wijnen, J.T., Clark, S.K., and Hodgson, S.V.

Subjects
Peutz-Jeghers syndrome -- Diagnosis, Peutz-Jeghers syndrome -- Care and treatment, Peutz-Jeghers syndrome -- Development and progression, Peutz-Jeghers syndrome -- Risk factors, Medical literature -- Analysis, Health
Published
2010

32. Analysis in the Prospective Lynch Syndrome Database identifies sarcoma as part of the Lynch syndrome tumor spectrum

Author

Dominguez-Valentin M., Sampson J. R., Moller P., Seppala T. T., Plazzer J. -P., Nakken S., Engel C., Aretz S., Jenkins M. A., Sunde L., Bernstein I., Capella G., Balaguer F., Thomas H., Evans D. G., Burn J., Greenblatt M., Hovig E., Nielsen M., de Vos tot Nederveen Cappel W. H., Sijmons R. H., Bertario L., Tibiletti M. G., Cavestro G. M., Lindblom A., Valle A. D., Lopez-Kostner F., Gluck N., Katz L. H., Heinimann K., Vaccaro C. A., Buttner R., Gorgens H., Holinski-Feder E., Morak M., Holzapfel S., Huneburg R., von Knebel Doeberitz M., Loeffler M., Rahner N., Weitz J., Steinke-Lange V., ten Broeke S. W., Schmiegel W., Vangala D., Pylvanainen K., Renkonen-Sinisalo L., Hopper J. L., Win A. K., Haile R. W., Lindor N. M., Gallinger S., Le Marchand L., Newcomb P. A., Figueiredo J. C., Thibodeau S. N., Jensen L. H., Madsen M. B., Kroldrup L., Nilbert M., Moreira L., Sanchez A., Serra-Burriel M., Pineda M., Navarro M., Vidal J. B., Blanco I., Green K., Lalloo F., Crosbie E. J., Hill J., Denton O. G., Rodland E. A., Vasen H., Mints M., Neffa F., Esperon P., Alvarez K., Kariv R., Rosner G., Pinero T. A., Gonzalez M. L., Kalfayan P., Tjandra D., Winship I. M., Macrae F., Moslein G., Mecklin J. -P., Dominguez-Valentin, M., Sampson, J. R., Moller, P., Seppala, T. T., Plazzer, J. -P., Nakken, S., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., Hovig, E., Nielsen, M., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Bertario, L., Tibiletti, M. G., Cavestro, G. M., Lindblom, A., Valle, A. D., Lopez-Kostner, F., Gluck, N., Katz, L. H., Heinimann, K., Vaccaro, C. A., Buttner, R., Gorgens, H., Holinski-Feder, E., Morak, M., Holzapfel, S., Huneburg, R., von Knebel Doeberitz, M., Loeffler, M., Rahner, N., Weitz, J., Steinke-Lange, V., ten Broeke, S. W., Schmiegel, W., Vangala, D., Pylvanainen, K., Renkonen-Sinisalo, L., Hopper, J. L., Win, A. K., Haile, R. W., Lindor, N. M., Gallinger, S., Le Marchand, L., Newcomb, P. A., Figueiredo, J. C., Thibodeau, S. N., Jensen, L. H., Madsen, M. B., Kroldrup, L., Nilbert, M., Moreira, L., Sanchez, A., Serra-Burriel, M., Pineda, M., Navarro, M., Vidal, J. B., Blanco, I., Green, K., Lalloo, F., Crosbie, E. J., Hill, J., Denton, O. G., Rodland, E. A., Vasen, H., Mints, M., Neffa, F., Esperon, P., Alvarez, K., Kariv, R., Rosner, G., Pinero, T. A., Gonzalez, M. L., Kalfayan, P., Tjandra, D., Winship, I. M., Macrae, F., Moslein, G., and Mecklin, J. -P.

Subjects
Male, Adult, Oncology, Cancer Research, 2019-20 coronavirus outbreak, medicine.medical_specialty, sarcoma, Databases, Factual, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sarcoma/diagnosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Aged, business.industry, Sarcoma, Syndrome, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, MSH2, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis, Female, 030211 gastroenterology & hepatology, business
Published
2020

33. Pruritus characteristics in a large Italian cohort of psoriatic patients

Author

Damiani, G., Cazzaniga, S., Conic, R. R. Z., Naldi, L., Griseta, V., Miracapillo, A., Azzini, M., Mocci, L., Michelini, M., Offidani, A., Bernardini, L., Campanati, A., Ricotti, G., Giacchetti, A., Norat, M., Gualco, F., Castelli, A., Cuccia, A., Diana, A., Roncarolo, G., Belli, M. A., Baldassarre, M. A., Santoro, G., Vena, G. A., Lo Console, F., Filotico, R., Mastrandrea, V., Brunetti, B., Musumeci, F., Carrabba, E., Dal Mas, P., Annicchiarico, F., Benvegnu, B., Spaziani, G., Cusano, F., Saletta Iannazzone, S., Galluccio, A., Pezza, M., Marchesi, L., Imberti, G., Reseghetti, A., Barbera, C., Reggiani, M., Lanzoni, A., Patrizi, A., Bardazzi, F., Antonucci, A., De Tommaso, S., Wallnofer, W., Ingannamorte, F., Calzavara-Pinton, P., Iannazzi, S., Zane, C., Capezzera, R., Bassisi, S., Rossi, M. T., Altamura, V., Vigl, W., Nobile, C., Aste, N., Murgia, S., Mugheddu, C., Scuderi, G., Baglieri, F., Di Dio, C., Cilioni Grilli, E., Mastronardi, C., Agnusdei, C. P., Antrilli, A., Aulisa, L., Raimondo, U., Scotto di Luzio, G., Battarra, V. C., Farro, P., Plaitano, R., Micali, G., Musumeci, M. L., Massimino, D., Li Calzi, M., La Greca, S., Pettinato, M., Sapienza, G., Valenti, G., De Giacomo, P. F., Amico, Arcangeli, F., Brunelli, D., Ghetti, E., Tulli, A., Assi, G., Amerio, P., Laria, G., Prestinari, F., Spadafora, S., Coppola, M., Caresana, G., Pezzarossa, E., Felisi, C., Donato, L., Bertero, M., Musso, L., Pa lazzini, S., Bruscino, P., Agozzino, U. C., Ottaviani, M., Simoncini, C., Virgili, A., Osti, F., Fabbri, P., Volpi, W., Caproni, M., Lotti, T., Prignano, F., Buggiani, G., Troiano, M., Fenizi, G., Altobella, A., Amoruso, A., Condello, M., Goffredo, A., Righini, M. G., Alessandrini, F., Satolli, F., Zampetti, M., Bertani, E., Fossati, S., Parodi, A., Burlando, M., Fiorucci, C., Nigro, A., Ghigliotti, G., Massone, L., Moise, G. M., Serrai, M., Cannata, G., Campagnoli, A. M., Daly, M., Leporati, C., Peila, R., Filosa, G., Bugatti, L., Nicolini, M., Nazzari, G., Cestari, R., Anastasio, F., Larussa, F. M., Pollice, N., De Francesco, F., Mazzocchetti, G., Peris, K., Fargnoli, M. C., Di Cesare, A., De Angelis, L., Flati, G., Biamonte, A. S., Quarta, G., Congedo, M., Carcaterra, A., Strippoli, D., Fideli, D., Marsili, F., Celli, M., Ceccarini, M., Bachini, L., D'Oria, M., Schirripa, V., De Filippi, C., Martini, P., Lapucci, E., Mazzatenta, C., Ghilardi, A., Simonacci, M., Bettacchi, A., Gasco, R., Zanca, A., Battistini, S., Dattola, S., Vernaci, R., Postorino, F., Zampieri, P. F., Padovan, C., Gonzalez Intchaurraga, M. A., Ladurner, J., Guarneri, B., Cannavo, S., Manfre, C., Borgia, F., Puglisi Guerra, A., Cattaneo, A., Carrera, C., Fracchiolla, C., Mozzanica, N., Prezzemolo, L., Menni, S., Lodi, A., Martino, P., Monti, M., Mancini, L., Sacrini, F., Altomare, G. F., Taglioni, M., Lovati, C., Mercuri, S. R., Schiesari, G., Giannetti, A., Conti, A., Lasagni, C., Greco, M., Ronsini, G., Schianchi, S., Fiorentini, C., Niglietta, S., Maglietta, R., Padalino, C., Crippa, D., Pini, M., Rossi, E., Tosi, D., Armas, M., Ruocco, V., Ayala, F., Balato, N., Gaudiello, F., Cimmino, G. F., Monfrecola, G., Gallo, L., Argenziano, G., Fulgione, E., Berruti, G., Ceparano, S., De Michele, I., Giorgiano, D., Leigheb, G., Deledda, S., Peserico, A., Alaibac, M., Piaserico, S., Schiesari, L., Dan, G., Mattei, I., Oro, E., Arico, M., Bongiorno, M. R., Angileri, R., Amato, S., Todaro, F., Milioto, M., Bellastro, R., Di Nuzzo, S., De Panfilis, G., Zanni, M., Borroni, G., Cananzi, R., Brazzelli, V., Lisi, P., Stingeni, L., Hansel, K., Pierfelice, V., Donelli, S., Rastelli, D., Gasperini, M., Barachini, P., Cecchi, R., Bartoli, L., Pavesi, M., De Paola, S., Corradin, M. T., Ricciuti, F., Piccirillo, A., Viola, L., Tataranni, M., Mautone, M. G., Lo Scocco, G., Niccoli, M. C., Brunasso Vernetti, A. M. G., Gaddoni, G., Resta, F., Casadio, M. C., Arcidiaco, M. C., Luvara, M. C., Albertini, G., Di Lernia, V., Guareschi, E., Catrani, S., Morri, M., De Simone, C., D'Agostino, M., Agostino, I., Calvieri, S., Cantoresi, F., Richetta, A., Sorgi, P., Carnevale, C., Nicolucci, F., Berardesca, E., Ardigo, M., De Felice, C., Gubinelli, E., Talamonti, M., Camplone, G., Cruciani, G., Riccardi, F., Barbati, R., Zumiani, G., Pagani, W., Malagoli, P. G., Pellicano, R., Donadio, D., Di Vito, C., Cottoni, F., Montesu, M. A., Pirodda, C., Addis, G., Marongiu, P., Farris, A., Cacciapuoti, M., Verrini, A., Desirello, G., Gnone, M., Fimiani, M., Pellegrino, M., Castelli, G., Zappala, L., Sesana, G., Ingordo, V., Vozza, E., Di Giuseppe, D., Fasciocco, D., Nespoli, P., Papini, M., Cicoletti, M., Bernengo, M. G., Ortoncelli, M., Bonvicino, A., Capella, G., Doveil, G. C., Forte, M., Peroni, A., Salomone, B., Savoia, P., Pippione, M., Zichichi, L., Frazzitta, M., De Luca, G., Tasin, L., Simonetto, D., Ros, S., Trevisan, G., Patamia, M., Miertusova, S., Patrone, P., Frattasio, A., Piccirillo, F., La Spina, S., Di Gaetano, L., Marzocchi, V., Motolese, A., Venturi, C., Gai, F., Pasquinucci, S., Bellazzi, R. M., Silvestri, T., Girolomoni, G., Gisondi, P., Veller Fornasa, C., Trevisan, G. P., Damiani G., Cazzaniga S., Conic R.R.Z., Naldi L., Griseta V., Miracapillo A., Azzini M., Mocci L., Michelini M., Offidani A., Bernardini L., Campanati A., Ricotti G., Giacchetti A., Norat M., Gualco F., Castelli A., Cuccia A., Diana A., Roncarolo G., Belli M.A., Baldassarre M.A., Santoro G., Vena G.A., Lo Console F., Filotico R., Mastrandrea V., Brunetti B., Musumeci F., Carrabba E., Dal Mas P., Annicchiarico F., Benvegnu B., Spaziani G., Cusano F., Saletta Iannazzone S., Galluccio A., Pezza M., Marchesi L., Imberti G., Reseghetti A., Barbera C., Reggiani M., Lanzoni A., Patrizi A., Bardazzi F., Antonucci A., De Tommaso S., Wallnofer W., Ingannamorte F., Calzavara-Pinton P., Iannazzi S., Zane C., Capezzera R., Bassisi S., Rossi M.T., Altamura V., Vigl W., Nobile C., Aste N., Murgia S., Mugheddu C., Scuderi G., Baglieri F., Di Dio C., Cilioni Grilli E., Mastronardi C., Agnusdei C.P., Antrilli A., Aulisa L., Raimondo U., Scotto di Luzio G., Battarra V.C., Farro P., Plaitano R., Micali G., Musumeci M.L., Massimino D., Li Calzi M., La Greca S., Pettinato M., Sapienza G., Valenti G., De Giacomo P.F., Amico, Arcangeli F., Brunelli D., Ghetti E., Tulli A., Assi G., Amerio P., Laria G., Prestinari F., Spadafora S., Coppola M., Caresana G., Pezzarossa E., Felisi C., Donato L., Bertero M., Musso L., Pa lazzini S., Bruscino P., Agozzino U.C., Ottaviani M., Simoncini C., Virgili A., Osti F., Fabbri P., Volpi W., Caproni M., Lotti T., Prignano F., Buggiani G., Troiano M., Fenizi G., Altobella A., Amoruso A., Condello M., Goffredo A., Righini M.G., Alessandrini F., Satolli F., Zampetti M., Bertani E., Fossati S., Parodi A., Burlando M., Fiorucci C., Nigro A., Ghigliotti G., Massone L., Moise G.M., Serrai M., Cannata G., Campagnoli A.M., Daly M., Leporati C., Peila R., Filosa G., Bugatti L., Nicolini M., Nazzari G., Cestari R., Anastasio F., Larussa F.M., Pollice N., De Francesco F., Mazzocchetti G., Peris K., Fargnoli M.C., Di Cesare A., De Angelis L., Flati G., Biamonte A.S., Quarta G., Congedo M., Carcaterra A., Strippoli D., Fideli D., Marsili F., Celli M., Ceccarini M., Bachini L., D'Oria M., Schirripa V., De Filippi C., Martini P., Lapucci E., Mazzatenta C., Ghilardi A., Simonacci M., Bettacchi A., Gasco R., Zanca A., Battistini S., Dattola S., Vernaci R., Postorino F., Zampieri P.F., Padovan C., Gonzalez Intchaurraga M.A., Ladurner J., Guarneri B., Cannavo S., Manfre C., Borgia F., Puglisi Guerra A., Cattaneo A., Carrera C., Fracchiolla C., Mozzanica N., Prezzemolo L., Menni S., Lodi A., Martino P., Monti M., Mancini L., Sacrini F., Altomare G.F., Taglioni M., Lovati C., Mercuri S.R., Schiesari G., Giannetti A., Conti A., Lasagni C., Greco M., Ronsini G., Schianchi S., Fiorentini C., Niglietta S., Maglietta R., Padalino C., Crippa D., Pini M., Rossi E., Tosi D., Armas M., Ruocco V., Ayala F., Balato N., Gaudiello F., Cimmino G.F., Monfrecola G., Gallo L., Argenziano G., Fulgione E., Berruti G., Ceparano S., De Michele I., Giorgiano D., Leigheb G., Deledda S., Peserico A., Alaibac M., Piaserico S., Schiesari L., Dan G., Mattei I., Oro E., Arico M., Bongiorno M.R., Angileri R., Amato S., Todaro F., Milioto M., Bellastro R., Di Nuzzo S., De Panfilis G., Zanni M., Borroni G., Cananzi R., Brazzelli V., Lisi P., Stingeni L., Hansel K., Pierfelice V., Donelli S., Rastelli D., Gasperini M., Barachini P., Cecchi R., Bartoli L., Pavesi M., De Paola S., Corradin M.T., Ricciuti F., Piccirillo A., Viola L., Tataranni M., Mautone M.G., Lo Scocco G., Niccoli M.C., Brunasso Vernetti A.M.G., Gaddoni G., Resta F., Casadio M.C., Arcidiaco M.C., Luvara M.C., Albertini G., Di Lernia V., Guareschi E., Catrani S., Morri M., De Simone C., D'Agostino M., Agostino I., Calvieri S., Cantoresi F., Richetta A., Sorgi P., Carnevale C., Nicolucci F., Berardesca E., Ardigo M., De Felice C., Gubinelli E., Talamonti M., Camplone G., Cruciani G., Riccardi F., Barbati R., Zumiani G., Pagani W., Malagoli P.G., Pellicano R., Donadio D., Di Vito C., Cottoni F., Montesu M.A., Pirodda C., Addis G., Marongiu P., Farris A., Cacciapuoti M., Verrini A., Desirello G., Gnone M., Fimiani M., Pellegrino M., Castelli G., Zappala L., Sesana G., Ingordo V., Vozza E., Di Giuseppe D., Fasciocco D., Nespoli P., Papini M., Cicoletti M., Bernengo M.G., Ortoncelli M., Bonvicino A., Capella G., Doveil G.C., Forte M., Peroni A., Salomone B., Savoia P., Pippione M., Zichichi L., Frazzitta M., De Luca G., Tasin L., Simonetto D., Ros S., Trevisan G., Patamia M., Miertusova S., Patrone P., Frattasio A., Piccirillo F., La Spina S., Di Gaetano L., Marzocchi V., Motolese A., Venturi C., Gai F., Pasquinucci S., Bellazzi R.M., Silvestri T., Girolomoni G., Gisondi P., Veller Fornasa C., and Trevisan G.P.

Subjects
Male, Cross-sectional study, Severity of Illness Index, Cohort Studies, 030207 dermatology & venereal diseases, 0302 clinical medicine, Risk Factors, education, itch, pruritus, psoriasis, pustular psoriasis, treatment, Adolescent, Adult, Cross-Sectional Studies, Educational Status, Facial Dermatoses, Female, Foot Dermatoses, Genitalia, Hand Dermatoses, Humans, Italy, Middle Aged, Pruritus, Psoriasis, Registries, Sex Factors, Young Adult, Epidemiology, Young adult, skin and connective tissue diseases, Settore MED/33 - MALATTIE APPARATO LOCOMOTORE, Infectious Diseases, 030220 oncology & carcinogenesis, Cohort, PRURITIS EPIDEMIOLOGY, Settore MED/35 - MALATTIE CUTANEE E VENEREE, Cohort study, medicine.medical_specialty, PSORIAS, Dermatology, Article, 03 medical and health sciences, Pharmacotherapy, Settore MED/35, Severity of illness, medicine, business.industry, medicine.disease, Pruritus,Itch sensation, business
Abstract

Background: Psoriasis (Ps) is a chronic systemic autoimmune disease associated with pruritus in 64–98% of patients. However, few modestly sized studies assess factors associated with psoriatic pruritus. Objective: To investigate factors associated with Ps pruritus intensity. Methods: Psoriasis patients 18years or older seen in one of 155 centres in Italy between September 2005 and 2009 were identified from the Italian PsoCare registry. Patients without cutaneous psoriasis and those with missed information on pruritus were excluded. Results: We identified 10802 patients, with a mean age 48.8±14.3years. Mild itch was present in 33.2% of patients, moderate in 34.4%, severe in 18.7% and very severe in 13.7%. Higher itch intensity was associated with female gender, lower educational attainment compared to university degree, pustular psoriasis, psoriasis on the head, face, palmoplantar areas, folds and genitalia, more severe disease, disease duration

Published
2019

34. Guidelines for the clinical management of familial adenomatous polyposis (FAP)

Author

Vasen, H.F.A., Moslein, G., Alonso, A., Aretz, S., Bernstein, I., Bertario, L., Blanco, I., Bulow, S., Burn, J., Capella, G., Colas, C., Engel, C., Frayling, I., Friedl, W., Hes, F.J., Hodgson, S., Jarvinen, H., Mecklin, J.-P., Moller, P., Myrhoi, T., Nagengast, F.M., Parc, Y., Phillips, R., Clark, S.K., Ponz de Leon, M., Renkonen-Sinisalo, L., Sampson, J.R., Stormorken, A., Tejpar, S., Thomas, H.J.W., and Wijnen, J.

Subjects
Polyposis, Familial -- Care and treatment, Practice guidelines (Medicine) -- Evaluation, Colorectal cancer -- Risk factors, Colorectal cancer -- Prevention, Health
Published
2008

35. Role ofPOLEandPOLD1in familial cancer

Author

Mur, P, Garcia-Mulero, S, del Valle, J, Magraner-Pardo, L, Vidal, A, Pineda, M, Cinnirella, G, Martin-Ramos, E, Pons, T, Lopez-Doriga, A, Belhadj, S, Feliubadalo, L, Munoz-Torres, PM, Navarro, M, Grau, E, Darder, E, Llort, G, Sanz, J, Cajal, TRY, Balmana, J, Brunet, J, Moreno, V, Piulats, JM, Matias-Guiu, X, Sanz-Pamplona, R, Aligue, R, Capella, G, Lazaro, C, and Valle, L

Subjects
hereditary colorectal cancer, ultramutated phenotype, exonuclease domain, polymerase proofreading-associated polyposis, PPAP
Abstract

Purpose Germline pathogenic variants in the exonuclease domain (ED) of polymerasesPOLEandPOLD1predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence ofPOLEandPOLD1variants in hereditary cancer are evaluated in this study. Methods POLEandPOLD1were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics). Cosegregation and case-control studies, yeast-based functional assays, and tumor mutational analyses were performed for variant interpretation. Results Twelve ED missense variants, 6 loss-of-function, and 23 outside-ED predicted-deleterious missense variants, all with population allele frequencies

Published
2020

36. Comprehensive analysis and ACMG-based classification ofCHEK2variants in hereditary cancer patients

Author

Vargas-Parra, G, del Valle, J, Rofes, P, Gausachs, M, Stradella, A, Moreno-Cabrera, JM, Velasco, A, Tornero, E, Menendez, M, Munoz, X, Iglesias, S, Lopez-Doriga, A, Azuara, D, Campos, O, Cuesta, R, Darder, E, de Cid, R, Gonzalez, S, Teule, A, Navarro, M, Brunet, J, Capella, G, Pineda, M, Feliubadalo, L, and Lazaro, C

Subjects
hereditary cancer, low penetrance, molecular diagnosis, variant classification, CHEK2, risk allele
Abstract

CHEK2variants are associated with intermediate breast cancer risk, among other cancers. We aimed to comprehensively describeCHEK2variants in a Spanish hereditary cancer (HC) cohort and adjust the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. First, threeCHEK2frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients. After, the wholeCHEK2coding region was analyzed by next-generation sequencing in 1848 prospective patients with HC suspicion. We refined ACMG-AMP criteria and applied different combined rules to classifyCHEK2variants and define risk alleles. We identified 10CHEK2null variants, 6 missense variants with discordant interpretation in ClinVar database, and 35 additional variants of unknown significance. Twelve variants were classified as (likely)-pathogenic; two can also be considered "established risk-alleles" and one as "likely risk-allele." The prevalence of (likely)-pathogenic variants in the HC cohort was 0.8% (1.3% in breast cancer patients and 1.0% in hereditary nonpolyposis colorectal cancer patients). Here, we provide ACMG adjustment guidelines to classifyCHEK2variants. We hope that this study would be useful for variant classification of other genes with low effect variants.

Published
2020

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

Author

Damaso, E, Gonzalez-Acosta, M, Vargas-Parra, G, Navarro, M, Balmana, J, Ramon y Cajal, T, Tuset, N, Thompson, BA, Marin, F, Fernandez, A, Gomez, C, Velasco, A, Solanes, A, Iglesias, S, Urgel, G, Lopez, C, del Valle, J, Campos, O, Santacana, M, Matias-Guiu, X, Lazaro, C, Valle, L, Brunet, J, Pineda, M, Capella, G, Damaso, E, Gonzalez-Acosta, M, Vargas-Parra, G, Navarro, M, Balmana, J, Ramon y Cajal, T, Tuset, N, Thompson, BA, Marin, F, Fernandez, A, Gomez, C, Velasco, A, Solanes, A, Iglesias, S, Urgel, G, Lopez, C, del Valle, J, Campos, O, Santacana, M, Matias-Guiu, X, Lazaro, C, Valle, L, Brunet, J, Pineda, M, and Capella, G

Abstract

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. Mutational analysis of 26 colorectal cancer (CRC)-associated genes was performed. Pathogenicity of MMR variants was assessed by splicing and multifactorial likelihood analyses. Genome-wide methylome analysis was performed by the Infinium Human Methylation 450K Bead Chip. The multigene panel analysis revealed the presence of two MMR gene truncating mutations not previously found. Of a total of 15 additional MMR variants identified, five -present in 6 unrelated individuals- were reclassified as pathogenic. In addition, 13 predicted deleterious variants in other CRC-predisposing genes were found in 12 probands. Methylome analysis detected one constitutional MLH1 epimutation, but no additional differentially methylated regions were identified in LLS compared to LS patients or cancer-free individuals. In conclusion, the use of an ad-hoc designed gene panel combined with pathogenicity assessment of variants allowed the identification of deleterious MMR mutations as well as new LLS candidate causal genes. Constitutional epimutations in non-LS-associated genes are not responsible for LLS.

Published
2020

38. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database (vol 22, pg 15, 2020)

Author

Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buttner, R, Gorgens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Huneburg, R, Knebel Doeberitz, MV, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moslein, G, Mecklin, J-P, Nielsen, M, Moller, P, Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buttner, R, Gorgens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Huneburg, R, Knebel Doeberitz, MV, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moslein, G, Mecklin, J-P, Nielsen, M, and Moller, P

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

39. Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database

Author

Dominguez-Valentin, M, Seppala, TT, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Vidal, JB, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Sampson, JR, Ryan, NAJ, Evans, DG, Moller, P, Crosbie, EJ, Dominguez-Valentin, M, Seppala, TT, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauss, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Vidal, JB, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Sampson, JR, Ryan, NAJ, Evans, DG, Moller, P, and Crosbie, EJ

Abstract

PURPOSE: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. METHODS: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. RESULTS: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (~90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35-55 years). CONCLUSIONS: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.

Published
2020

40. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

Author

Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos Tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moeslein, G, Mecklin, J-P, Nielsen, M, Moller, P, Dominguez-Valentin, M, Sampson, JR, Seppala, TT, ten Broeke, SW, Plazzer, J-P, Nakken, S, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, Hovig, E, de Vos Tot Nederveen Cappel, WH, Sijmons, RH, Bertario, L, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Gluck, N, Katz, LH, Heinimann, K, Vaccaro, CA, Buettner, R, Goergens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hueneburg, R, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schackert, HK, Steinke-Lange, V, Schmiegel, W, Vangala, D, Pylvanainen, K, Renkonen-Sinisalo, L, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Wadt, K, Therkildsen, C, Okkels, H, Ketabi, Z, Moreira, L, Sanchez, A, Serra-Burriel, M, Pineda, M, Navarro, M, Blanco, I, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Denton, OG, Frayling, IM, Rodland, EA, Vasen, H, Mints, M, Neffa, F, Esperon, P, Alvarez, K, Kariv, R, Rosner, G, Pinero, TA, Gonzalez, ML, Kalfayan, P, Tjandra, D, Winship, IM, Macrae, F, Moeslein, G, Mecklin, J-P, Nielsen, M, and Moller, P

Abstract

PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. CONCLUSION: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

Published
2020

42. POST-COLONOSCOPY COLORECTAL CANCER IN LYNCH SYNDROME IS ASSOCIATED WITH QUALITY ISSUES DURING SURVEILLANCE

Author

Sanchez Garcia, A, additional, Navarro, M, additional, Roos, VH, additional, Pineda, M, additional, Caballol, B, additional, Moreno, L, additional, Ocaña, T, additional, Rodriguez-Moranta, F, additional, Rodriguez-Alonso, L, additional, Cajal, TRy, additional, Llort, G, additional, Pico, MD, additional, Jover, R, additional, Lopez Fernandez, Adria, additional, Martinez de Castro, E, additional, Lopez-Arias, MJ, additional, Alvarez, C, additional, Bessa, X, additional, Rivas, L, additional, Cubiella, J, additional, Rodriguez-Alcalde, D, additional, Dacal, A, additional, Herraiz, M, additional, Garau, C, additional, Bujanda, L, additional, Cid, L, additional, Poves, C, additional, Garzon, M, additional, Pizarro, A, additional, Salces, I, additional, Ponce, M, additional, Carrillo-Palau, M, additional, Aguirre, E, additional, Saperas, E, additional, Suarez, A, additional, Piñol, V, additional, Carballal, S, additional, Rivero-Sanchez, L, additional, Balmaña, J, additional, Brunet, J, additional, Castells, A, additional, Dekker, E, additional, Pellise, M, additional, Capella, G, additional, Serra-Buriel, M, additional, Moreira, L, additional, and Balaguer, F, additional

Published
2020
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43. 128TiP VCN-01 plus durvalumab in subjects with recurrent/metastatic head & neck squamous cell carcinoma (R/M HNSCC): Phase I clinical trial

Author

Jove, M., primary, Braña, I., additional, Taberna, M., additional, Hernando-Calvo, A., additional, Castro, J. Brenes, additional, Garralda, E., additional, Serrahima, M. Plana, additional, Pujol, M. Maños, additional, Capella, G., additional, Alemany, R., additional, Blasi, E., additional, Blasco, C., additional, Piqueras, M. Cascallo, additional, and Nin, R. Mesia, additional

Published
2019
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45. Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes

Author

Vos, JR, Giepmans, L, Rohl, C, Geverink, N, Hoogerbrugge, N, Ligtenberg, M, Kets, M, Sijmons, R, Evans, G, Woodward, E, Tischkowitz, M, Maher, E, Steinke-Lange, V, Holinski-Feder, E, Frebourg, T, Houdayer, C, Ferner, RE, Lubinski, J, Ertmanska, K, Lagercrantz, SB, Tham, E, Guillermo, IB, Capella, G, Vidal, JB, Lazaro, C (Conxi), Balmana, J, Bours, V, Legius, E, Wolkenstein, P, Melegh, B, Oliveira, C, Teixeira, M, Poppe, B, Claes, K, Hernandez, HS, Aretz, AWM, Spier, I, Oostenbrink, Rianne, Krajc, M, Blatnik, A, Schrock, E, Peltonen, S, Hietala, M, Ern, G, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Erasmus School of Health Policy & Management, Pediatrics, and Legius, Eric

Subjects
0301 basic medicine, Cancer Research, Pediatrics, Databases, Factual, Colorectal cancer, International Cooperation, 030105 genetics & heredity, Medical Oncology, GUIDELINES, COLORECTAL-CANCER, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Epidemiology, Medicine and Health Sciences, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Registries, Genetics (clinical), Syndrome, Quality Improvement, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Rare diseases, Europe, Oncology, 030220 oncology & carcinogenesis, Clinical Competence, Hereditary diffuse gastric cancer, medicine.medical_specialty, Short Communication, European Reference Network, behavioral disciplines and activities, Time-to-Treatment, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Cross border health care, SDG 3 - Good Health and Well-being, Genetic, Neoplastic Syndromes, Hereditary, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Genetic Testing, Neurofibromatosis, Information Services, business.industry, Information Dissemination, Remote Consultation, Cancer, medicine.disease, PREVENTION, Hereditary cancer, Li–Fraumeni syndrome, business, Rare disease
Abstract

Approximately 27-36 million patients in Europe have one of the ~ 5.000-8.000 known rare diseases. These patients often do not receive the care they need or they have a substantial delay from diagnosis to treatment. In March 2017, twenty-four European Reference Networks (ERNs) were launched with the aim to improve the care for these patients through cross border healthcare, in a way that the medical knowledge and expertise travels across the borders, rather than the patients. It is expected that through the ERNs, European patients with a rare disease get access to expert care more often and more quickly, and that research and guideline development will be accelerated resulting in improved diagnostics and therapies. The ERN on Genetic Tumour Risk Syndromes (ERN GENTURIS) aims to improve the identification, genetic diagnostics, prevention of cancer, and treatment of European patients with a genetic predisposition for cancer. The ERN GENTURIS focuses on syndromes such as hereditary breast cancer, hereditary colorectal cancer and polyposis, neurofibromatosis and more rare syndromes e.g. PTEN Hamartoma Tumour Syndrome, Li Fraumeni Syndrome and hereditary diffuse gastric cancer. ispartof: Familial Cancer vol:18 issue:2 pages:281-284 ispartof: location:Netherlands status: published

Published
2019

48. The Apparent Genetic Anticipation in PMS2-Associated Lynch Syndrome Families Is Explained by Birth-cohort Effect

Author

Broeke, S.W. ten, Rodriguez-Girondo, M., Suerink, M., Aretz, S., Bernstein, I., Capella, G., Engel, C., Gomez-Garcia, E.B., Hest, L.P. van, Doeberitz, M. von Knebel, Lagerstedt-Robinson, K., Letteboer, T.G., Moller, P., Os, T.A. van, Pineda, M., Rahner, N., Olderode-Berends, M.J., Salome, J. von, Schackert, H.K., Spruijt, L., Steinke-Lange, V., Wagner, A., Tops, C.M., Nielsen, M., Broeke, S.W. ten, Rodriguez-Girondo, M., Suerink, M., Aretz, S., Bernstein, I., Capella, G., Engel, C., Gomez-Garcia, E.B., Hest, L.P. van, Doeberitz, M. von Knebel, Lagerstedt-Robinson, K., Letteboer, T.G., Moller, P., Os, T.A. van, Pineda, M., Rahner, N., Olderode-Berends, M.J., Salome, J. von, Schackert, H.K., Spruijt, L., Steinke-Lange, V., Wagner, A., Tops, C.M., and Nielsen, M.

Abstract

Contains fulltext : 206727.pdf (publisher's version ) (Closed access), BACKGROUND: PMS2-associated Lynch syndrome is characterized by a relatively low colorectal cancer penetrance compared with other Lynch syndromes. However, age at colorectal cancer diagnosis varies widely, and a strong genetic anticipation effect has been suggested for PMS2 families. In this study, we examined proposed genetic anticipation in a sample of 152 European PMS2 families. METHODS: The 152 families (637 family members) that were eligible for analysis were mainly clinically ascertained via clinical genetics centers. We used weighted Cox-type random effects model, adjusted by birth cohort and sex, to estimate the generational effect on the age of onset of colorectal cancer. Probands and young birth cohorts were excluded from the analyses. Weights represented mutation probabilities based on kinship coefficients, thus avoiding testing bias. RESULTS: Family data across three generations, including 123 colorectal cancers, were analyzed. When compared with the first generation, the crude HR for anticipation was 2.242 [95% confidence interval (CI), 1.162-4.328] for the second generation and 2.644 (95% CI, 1.082-6.464) for the third generation. However, after correction for birth cohort and sex, the effect vanished [HR = 1.302 (95% CI, 0.648-2.619) and HR = 1.074 (95% CI, 0.406-2.842) for second and third generations, respectively]. CONCLUSIONS: Our study did not confirm previous reports of genetic anticipation in PMS2-associated Lynch syndrome. Birth-cohort effect seems the most likely explanation for observed younger colorectal cancer diagnosis in subsequent generations, particularly because there is currently no commonly accepted biological mechanism that could explain genetic anticipation in Lynch syndrome. IMPACT: This new model for studying genetic anticipation provides a standard for rigorous analysis of families with dominantly inherited cancer predisposition.

Published
2019

49. Cancer Risks for PMS2-Associated Lynch Syndrome (vol 29, pg 2961, 2018)

Author

ten Broeke, SW, van der Klift, HM, Tops, CMJ, Aretz, S, Bernstein, I, Buchanan, DD, de la Chapelle, A, Capella, G, Clendenning, M, Engel, C, Gallinger, S, Garcia, EG, Figueiredo, JC, Haile, R, Hampel, HL, van Hest, L, Hopper, JL, Hoogerbrugge, N, Doeberitz, MVK, Le Marchand, L, Letteboer, TGW, Jenkins, MA, Lindblom, A, Lindor, NM, Mensenkamp, AR, Moller, P, Newcomb, PA, van Os, TAM, Pearlman, R, Pineda, M, Rahner, N, Redeker, EJW, Olderode-Berends, MJW, Rosty, C, Schackert, HK, Scott, R, Senter, L, Spruijt, L, Steinke-Lange, V, Suerink, M, Thibodeau, S, Vos, YJ, Wagner, A, Winship, I, Hes, FJ, Vasen, HFA, Wijnen, JT, Nielsen, M, Win, AK, ten Broeke, SW, van der Klift, HM, Tops, CMJ, Aretz, S, Bernstein, I, Buchanan, DD, de la Chapelle, A, Capella, G, Clendenning, M, Engel, C, Gallinger, S, Garcia, EG, Figueiredo, JC, Haile, R, Hampel, HL, van Hest, L, Hopper, JL, Hoogerbrugge, N, Doeberitz, MVK, Le Marchand, L, Letteboer, TGW, Jenkins, MA, Lindblom, A, Lindor, NM, Mensenkamp, AR, Moller, P, Newcomb, PA, van Os, TAM, Pearlman, R, Pineda, M, Rahner, N, Redeker, EJW, Olderode-Berends, MJW, Rosty, C, Schackert, HK, Scott, R, Senter, L, Spruijt, L, Steinke-Lange, V, Suerink, M, Thibodeau, S, Vos, YJ, Wagner, A, Winship, I, Hes, FJ, Vasen, HFA, Wijnen, JT, Nielsen, M, and Win, AK

Abstract

This corrects the article "Cancer Risks for PMS2-Associated Lynch Syndrome" in volume 36 on page 2961.

Published
2019

50. Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

Author

Dominguez-Valentin, M, Seppala, TT, Sampson, JR, Macrae, F, Winship, I, Evans, DG, Scott, RJ, Burn, J, Moeslein, G, Bernstein, I, Pylvanainen, K, Renkonen-Sinisalo, L, Lepistoe, A, Lindblom, A, Plazzer, J-P, Tjandra, D, Thomas, H, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Capella, G, Pineda, M, Navarro, M, Vidal, JB, Ronlund, K, Nielsen, RT, Yilmaz, M, Elvang, LL, Katz, L, Nielsen, M, ten Broeke, SW, Nakken, S, Hovig, E, Sunde, L, Kloor, M, Doeberitz, MVK, Ahadova, A, Lindor, N, Steinke-Lange, V, Holinski-Feder, E, Mecklin, J-P, Moller, P, Dominguez-Valentin, M, Seppala, TT, Sampson, JR, Macrae, F, Winship, I, Evans, DG, Scott, RJ, Burn, J, Moeslein, G, Bernstein, I, Pylvanainen, K, Renkonen-Sinisalo, L, Lepistoe, A, Lindblom, A, Plazzer, J-P, Tjandra, D, Thomas, H, Green, K, Lalloo, F, Crosbie, EJ, Hill, J, Capella, G, Pineda, M, Navarro, M, Vidal, JB, Ronlund, K, Nielsen, RT, Yilmaz, M, Elvang, LL, Katz, L, Nielsen, M, ten Broeke, SW, Nakken, S, Hovig, E, Sunde, L, Kloor, M, Doeberitz, MVK, Ahadova, A, Lindor, N, Steinke-Lange, V, Holinski-Feder, E, Mecklin, J-P, and Moller, P

Abstract

BACKGROUND: We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. METHODS: The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. RESULTS: Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5-2.5, 2.5-3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5-3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5-2.5, 2.5-3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). CONCLUSIONS: In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.

Published
2019

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