367 results on '"Sijmons, Rolf"'
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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
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Dominguez-Valentin, Mev, Haupt, Saskia, Seppälä, Toni T., Sampson, Julian R., Sunde, Lone, Bernstein, Inge, Jenkins, Mark A., Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Balaguer, Francesc, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Dębniak, Tadeusz, Fruscio, Robert, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Katz, Lior H., Laish, Ido, Vainer, Elez, Vaccaro, Carlos, Carraro, Dirce Maria, Monahan, Kevin, Half, Elizabeth, Stakelum, Aine, Winter, Des, Kennelly, Rory, Gluck, Nathan, Sheth, Harsh, Abu-Freha, Naim, Greenblatt, Marc, Rossi, Benedito Mauro, Bohorquez, Mabel, Cavestro, Giulia Martina, Lino-Silva, Leonardo S., Horisberger, Karoline, Tibiletti, Maria Grazia, Nascimento, Ivana do, Thomas, Huw, Rossi, Norma Teresa, Apolinário da Silva, Leandro, Zaránd, Attila, Ruiz-Bañobre, Juan, Heuveline, Vincent, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Peltomäki, Päivi, Therkildsen, Christina, Madsen, Mia Gebauer, Burgdorf, Stefan Kobbelgaard, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Schröck, Evelin, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, Redler, Silke, Büttner, Reinhard, Weitz, Jürgen, Pineda, Marta, Duenas, Nuria, Vidal, Joan Brunet, Moreira, Leticia, Sánchez, Ariadna, Hovig, Eivind, Nakken, Sigve, Green, Kate, Lalloo, Fiona, Hill, James, Crosbie, Emma, Mints, Miriam, Goldberg, Yael, Tjandra, Douglas, ten Broeke, Sanne W., Kariv, Revital, Rosner, Guy, Advani, Suresh H., Thomas, Lidiya, Shah, Pankaj, Shah, Mithun, Neffa, Florencia, Esperon, Patricia, Pavicic, Walter, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia Alejandra, Moslein, Gabriela, and Moller, Pål
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- 2023
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3. SEPT–GD: A decision tree to prioritise potential RNA splice variants in cardiomyopathy genes for functional splicing assays in diagnostics
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Alimohamed, Mohamed Z., Boven, Ludolf G., van Dijk, Krista K., Vos, Yvonne J., Hoedemaekers, Yvonne M., van der Zwaag, Paul A., Sijmons, Rolf H., Jongbloed, Jan D.H., Sikkema-Raddatz, Birgit, and Westers, Helga
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- 2023
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4. Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement
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Maller, Pal, Seppälä, Toni T., Ahadova, Aysel, Crosbie, Emma J., Holinski-Feder, Elke, Scott, Rodney, Haupt, Saskia, Möslein, Gabriela, Winship, Ingrid, Broeke, Sanne W. Bajwa-ten, Kohut, Kelly E., Ryan, Neil, Bauerfeind, Peter, Thomas, Laura E., Evans, D. Gareth, Aretz, Stefan, Sijmons, Rolf H., Half, Elizabeth, Heinimann, Karl, Horisberger, Karoline, Monahan, Kevin, Engel, Christoph, Cavestro, Giulia Martina, Fruscio, Robert, Abu-Freha, Naim, Zohar, Levi, Laghi, Luigi, Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Vaccaro, Carlos, Valle, Adriana Della, Rossi, Benedito Mauro, da Silva, Leandro Apolinário, de Oliveira Nascimento, Ivana Lucia, Rossi, Norma Teresa, DÄbniak, Tadeusz, Mecklin, Jukka-Pekka, Bernstein, Inge, Lindblom, Annika, Sunde, Lone, Nakken, Sigve, Heuveline, Vincent, Burn, John, Hovig, Eivind, Kloor, Matthias, Sampson, Julian R., and Dominguez-Valentin, Mev
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Aspirin ,Stochastic processes ,Colorectal cancer -- Genetic aspects -- Development and progression ,Immunotherapy ,Cancer -- Development and progression -- Genetic aspects ,Ovarian cancer -- Development and progression -- Genetic aspects ,Health - Abstract
The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an 'average sex 'or a pathogenic variant in an 'average Lynch syndrome gene' and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer., Author(s): Pal Maller[sup.1], Toni T. Seppälä[sup.2,3,4], Aysel Ahadova[sup.5,6,7], Emma J. Crosbie[sup.8,9], Elke Holinski-Feder[sup.10,11], Rodney Scott[sup.12], Saskia Haupt[sup.13,14], Gabriela Möslein[sup.15], Ingrid Winship[sup.16,17], Sanne W. Bajwa-ten Broeke[sup.18], Kelly E. Kohut[sup.19], Neil Ryan[sup.20,21], [...]
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- 2023
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5. Evaluation of a seven gene mutational profile as a prognostic factor in a population-based study of clear cell renal cell carcinoma
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van de Pol, Jeroen A. A., Ferronika, Paranita, Westers, Helga, van Engeland, Manon, Terpstra, Martijn M., Smits, Kim M., de Lange, Kim, van den Brandt, Piet A., Sijmons, Rolf H., Schouten, Leo J., and Kok, Klaas
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- 2022
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6. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium
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Møller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubiński, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Dębniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueñas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.
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- 2022
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7. Men with metastatic prostate cancer carrying a pathogenic germline variant in breast cancer genes: disclosure of genetic test results to relatives
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Genetica, Genetica Sectie Oncogenetica, Cancer, Genetica Klinische Genetica, Vlaming, Michiel, Ausems, Margreet G.E.M., Schijven, Gina, van Oort, Inge M., Kets, C. Marleen, Komdeur, Fenne L., van der Kolk, Lizet E., Oldenburg, Rogier A., Sijmons, Rolf H., Kiemeney, Lambertus A.L.M., Bleiker, Eveline M.A., Genetica, Genetica Sectie Oncogenetica, Cancer, Genetica Klinische Genetica, Vlaming, Michiel, Ausems, Margreet G.E.M., Schijven, Gina, van Oort, Inge M., Kets, C. Marleen, Komdeur, Fenne L., van der Kolk, Lizet E., Oldenburg, Rogier A., Sijmons, Rolf H., Kiemeney, Lambertus A.L.M., and Bleiker, Eveline M.A.
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- 2024
8. Men with metastatic prostate cancer carrying a pathogenic germline variant in breast cancer genes:disclosure of genetic test results to relatives
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Vlaming, Michiel, Ausems, Margreet G.E.M., Schijven, Gina, van Oort, Inge M., Kets, C. Marleen, Komdeur, Fenne L., van der Kolk, Lizet E., Oldenburg, Rogier A., Sijmons, Rolf H., Kiemeney, Lambertus A.L.M., Bleiker, Eveline M.A., Vlaming, Michiel, Ausems, Margreet G.E.M., Schijven, Gina, van Oort, Inge M., Kets, C. Marleen, Komdeur, Fenne L., van der Kolk, Lizet E., Oldenburg, Rogier A., Sijmons, Rolf H., Kiemeney, Lambertus A.L.M., and Bleiker, Eveline M.A.
- Abstract
Some patients with metastatic prostate cancer carry a pathogenic germline variant (PV) in a gene, that is mainly associated with an increased risk of breast cancer in women. If they test positive for such a PV, prostate cancer patients are encouraged to disclose the genetic test result to relatives who are at risk in case the carrier status changes the relatives’ medical care. Our study aimed to investigate how men who learned they carry a PV in BRCA1, BRCA2, PALB2, CHEK2 or ATM disclosed their carrier status to at-risk relatives and to assess the possible psychological burden for the carrier and their perception of the burden for relatives. In total, 23 men with metastatic prostate cancer carrying a PV completed the IRI questionnaire about family communication; 14 also participated in a semi-structured interview. Patients felt highly confident in discussing the genetic test result with relatives. The diagnosis of prostate cancer was experienced as a burden, whereas being informed about genetic testing results did in most cases not add to this burden. Two patients encountered negative experiences with family communication, as they considered the genetic test result to be more urgent than their relatives. This mixed-methods study shows that metastatic prostate cancer patients with a PV in genes mainly associated with increased risk of breast cancer feel well-equipped to communicate about this predisposition in their families. Carriers felt motivated to disclose their genetic test result to relatives. Most of them indicated that the disclosure was not experienced as a psychological burden.
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- 2024
9. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report
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Dominguez-Valentin, Mev, Crosbie, Emma J., Engel, Christoph, Aretz, Stefan, Macrae, Finlay, Winship, Ingrid, Capella, Gabriel, Thomas, Huw, Nakken, Sigve, Hovig, Eivind, Nielsen, Maartje, Sijmons, Rolf H., Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Mints, Miriam, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Green, Kate, Lalloo, Fiona, Hill, James, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Strauß, Hans-Georg, Tecklenburg, Johanna, Holinski-Feder, Elke, Steinke-Lange, Verena, Mecklin, Jukka-Pekka, Plazzer, John-Paul, Pineda, Marta, Navarro, Matilde, Vidal, Joan Brunet, Kariv, Revital, Rosner, Guy, Piñero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Ryan, Neil, ten Broeke, Sanne W., Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Burn, John, Greenblatt, Marc, de Vos tot Nederveen Cappel, Wouter H., Della Valle, Adriana, Lopez-Koestner, Francisco, Alvarez, Karin, Büttner, Reinhard, Görgens, Heike, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Weitz, Jürgen, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Auranen, Annika, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Denton, Oliver G., Rødland, Einar Andreas, Vasen, Hans, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Möslein, Gabriela, Sampson, Julian R., Evans, D. Gareth, Seppälä, Toni T., and Møller, Pål
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- 2021
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10. A rare large duplication of MLH1 identified in Lynch syndrome
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Kumar, Abhishek, Paramasivam, Nagarajan, Bandapalli, Obul Reddy, Schlesner, Matthias, Chen, Tianhui, Sijmons, Rolf, Dymerska, Dagmara, Golebiewska, Katarzyna, Kuswik, Magdalena, Lubinski, Jan, Hemminki, Kari, and Försti, Asta
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- 2021
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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
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Maller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, LubiÅski, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, DÄbniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueéas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.
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EPUB (Standard) -- Comparative analysis ,Colonoscopy -- Comparative analysis ,Colorectal cancer -- Comparative analysis ,Health - 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. Keywords: Lynch Syndrome, Epidemiology, Prevention, Penetrance, Colorectal cancer, Segregation analysis, Prospective, Incidence, Over-diagnosis, Colonoscopy, Author(s): Pål Maller[sup.1], Toni Seppälä[sup.2,3,4], James G. Dowty[sup.5], Saskia Haupt[sup.6,7], Mev Dominguez-Valentin[sup.1], Lone Sunde[sup.8,9], Inge Bernstein[sup.10,11], Christoph Engel[sup.12], Stefan Aretz[sup.13], Maartje Nielsen[sup.14], Gabriel Capella[sup.15], Dafydd Gareth Evans[sup.16], John Burn[sup.17], Elke [...]
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- 2022
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12. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
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Dominguez-Valentin, Mev, Sampson, Julian R., Seppälä, Toni T., ten Broeke, Sanne W., Plazzer, John-Paul, Nakken, Sigve, Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Thomas, Huw, Evans, D. Gareth, Burn, John, Greenblatt, Marc, Hovig, Eivind, de Vos tot Nederveen Cappel, Wouter H., Sijmons, Rolf H., Bertario, Lucio, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Köstner, Francisco, Gluck, Nathan, Katz, Lior H., Heinimann, Karl, Vaccaro, Carlos A., Büttner, Reinhard, Görgens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, Knebel Doeberitz, Magnus von, Loeffler, Markus, Rahner, Nils, Schackert, Hans K., Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Wadt, Karin, Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Moreira, Leticia, Sánchez, Ariadna, Serra-Burriel, Miquel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Denton, Oliver G., Frayling, Ian M., Rødland, Einar Andreas, Vasen, Hans, Mints, Miriam, Neffa, Florencia, Esperon, Patricia, Alvarez, Karin, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Tjandra, Douglas, Winship, Ingrid M., Macrae, Finlay, Möslein, Gabriela, Mecklin, Jukka-Pekka, Nielsen, Maartje, and Møller, Pål
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- 2020
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13. A functional assay–based procedure to classify mismatch repair gene variants in Lynch syndrome
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Drost, Mark, Tiersma, Yvonne, Thompson, Bryony A., Frederiksen, Jane H., Keijzers, Guido, Glubb, Dylan, Kathe, Scott, Osinga, Jan, Westers, Helga, Pappas, Lisa, Boucher, Kenneth M., Molenkamp, Siska, Zonneveld, José B., van Asperen, Christi J., Goldgar, David E., Wallace, Susan S., Sijmons, Rolf H., Spurdle, Amanda B., Rasmussen, Lene J., Greenblatt, Marc S., de Wind, Niels, and Tavtigian, Sean V.
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- 2019
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14. Characterization of rare germline variants in familial multiple myeloma
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Catalano, Calogerina, Paramasivam, Nagarajan, Blocka, Joanna, Giangiobbe, Sara, Huhn, Stefanie, Schlesner, Matthias, Weinhold, Niels, Sijmons, Rolf, de Jong, Mirjam, Langer, Christian, Preuss, Klaus-Dieter, Nilsson, Björn, Durie, Brian, Goldschmidt, Hartmut, Bandapalli, Obul Reddy, Hemminki, Kari, and Försti, Asta
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- 2021
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15. Reusability of coded data in the primary care electronic medical record: A dynamic cohort study concerning cancer diagnoses
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Sollie, Annet, Sijmons, Rolf H., Helsper, Charles, and Numans, Mattijs E.
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- 2017
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16. AXIN2‐related oligodontia‐colorectal cancer syndrome with cleft palate as a possible new feature
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Roht, Laura, primary, Hyldebrandt, Hanne K., additional, Stormorken, Astrid T., additional, Nordgarden, Hilde, additional, Sijmons, Rolf H., additional, Bos, Dennis K., additional, Riegert‐Johnson, Douglas, additional, Mantia‐Macklin, Sarah, additional, Ilves, Pilvi, additional, Muru, Kai, additional, Wojcik, Monica H., additional, Kahre, Tiina, additional, and Õunap, Katrin, additional
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- 2023
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17. 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
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Dominguez-Valentin, Mev, Haupt, Saskia, Seppälä, Toni T., Sampson, Julian R., Sunde, Lone, Bernstein, Inge, Jenkins, Mark A., Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Balaguer, Francesc, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Dębniak, Tadeusz, Fruscio, Robert, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Katz, Lior H., Laish, Ido, Vainer, Elez, Vaccaro, Carlos, Carraro, Dirce Maria, Monahan, Kevin, Half, Elizabeth, Stakelum, Aine, Winter, Des, Kennelly, Rory, Gluck, Nathan, Sheth, Harsh, Abu-Freha, Naim, Greenblatt, Marc, Rossi, Benedito Mauro, Bohorquez, Mabel, Cavestro, Giulia Martina, Lino-Silva, Leonardo S., Horisberger, Karoline, Tibiletti, Maria Grazia, Nascimento, Ivana do, Thomas, Huw, Rossi, Norma Teresa, Apolinário da Silva, Leandro, Zaránd, Attila, Ruiz-Bañobre, Juan, Heuveline, Vincent, Mecklin, Jukka Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Peltomäki, Päivi, Therkildsen, Christina, Madsen, Mia Gebauer, Burgdorf, Stefan Kobbelgaard, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Schröck, Evelin, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, Redler, Silke, Büttner, Reinhard, Weitz, Jürgen, Pineda, Marta, Duenas, Nuria, Vidal, Joan Brunet, Moreira, Leticia, Sánchez, Ariadna, Hovig, Eivind, Nakken, Sigve, Green, Kate, Lalloo, Fiona, Hill, James, Crosbie, Emma, Mints, Miriam, Goldberg, Yael, Tjandra, Douglas, ten Broeke, Sanne W., Kariv, Revital, Rosner, Guy, Advani, Suresh H., Thomas, Lidiya, Shah, Pankaj, Shah, Mithun, Neffa, Florencia, Esperon, Patricia, Pavicic, Walter, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia Alejandra, Moslein, Gabriela, Moller, Pål, Dominguez-Valentin, Mev, Haupt, Saskia, Seppälä, Toni T., Sampson, Julian R., Sunde, Lone, Bernstein, Inge, Jenkins, Mark A., Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Balaguer, Francesc, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Dębniak, Tadeusz, Fruscio, Robert, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Katz, Lior H., Laish, Ido, Vainer, Elez, Vaccaro, Carlos, Carraro, Dirce Maria, Monahan, Kevin, Half, Elizabeth, Stakelum, Aine, Winter, Des, Kennelly, Rory, Gluck, Nathan, Sheth, Harsh, Abu-Freha, Naim, Greenblatt, Marc, Rossi, Benedito Mauro, Bohorquez, Mabel, Cavestro, Giulia Martina, Lino-Silva, Leonardo S., Horisberger, Karoline, Tibiletti, Maria Grazia, Nascimento, Ivana do, Thomas, Huw, Rossi, Norma Teresa, Apolinário da Silva, Leandro, Zaránd, Attila, Ruiz-Bañobre, Juan, Heuveline, Vincent, Mecklin, Jukka Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Peltomäki, Päivi, Therkildsen, Christina, Madsen, Mia Gebauer, Burgdorf, Stefan Kobbelgaard, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Schröck, Evelin, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, Redler, Silke, Büttner, Reinhard, Weitz, Jürgen, Pineda, Marta, Duenas, Nuria, Vidal, Joan Brunet, Moreira, Leticia, Sánchez, Ariadna, Hovig, Eivind, Nakken, Sigve, Green, Kate, Lalloo, Fiona, Hill, James, Crosbie, Emma, Mints, Miriam, Goldberg, Yael, Tjandra, Douglas, ten Broeke, Sanne W., Kariv, Revital, Rosner, Guy, Advani, Suresh H., Thomas, Lidiya, Shah, Pankaj, Shah, Mithun, Neffa, Florencia, Esperon, Patricia, Pavicic, Walter, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia Alejandra, Moslein, Gabriela, and Moller, Pål
- 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 ca, 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 ac
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- 2023
18. ASO Visual Abstract: Surgical Oncologists and Nurses in Breast Cancer Care are Ready to Provide Pre-Test Genetic Counseling
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Genetica Sectie Oncogenetica, Genetica Klinische Genetica, MS CGO, Genetica, Genetica Sectie Genoomdiagnostiek, Cancer, Bokkers, Kyra, Bleiker, Eveline M A, Aalfs, Cora M, van Dalen, Thijs, Velthuizen, Mary E, Duijveman, Petra, Sijmons, Rolf H, Koole, Wouter, Schoenmaeckers, Ernst J P, Ausems, Margreet G E M, Genetica Sectie Oncogenetica, Genetica Klinische Genetica, MS CGO, Genetica, Genetica Sectie Genoomdiagnostiek, Cancer, Bokkers, Kyra, Bleiker, Eveline M A, Aalfs, Cora M, van Dalen, Thijs, Velthuizen, Mary E, Duijveman, Petra, Sijmons, Rolf H, Koole, Wouter, Schoenmaeckers, Ernst J P, and Ausems, Margreet G E M
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- 2023
19. Functional Studies on Primary Tubular Epithelial Cells Indicate a Tumor Suppressor Role of SETD2 in Clear Cell Renal Cell Carcinoma
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Li, Jun, Kluiver, Joost, Osinga, Jan, Westers, Helga, van Werkhoven, Maaike B, Seelen, Marc A., Sijmons, Rolf H., van den Berg, Anke, and Kok, Klaas
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- 2016
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20. PMS2-associated Lynch syndrome: Past, present and future
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Andini, Katarina D., primary, Nielsen, Maartje, additional, Suerink, Manon, additional, Helderman, Noah C., additional, Koornstra, Jan Jacob, additional, Ahadova, Aysel, additional, Kloor, Matthias, additional, Mourits, Marian J.E., additional, Kok, Klaas, additional, Sijmons, Rolf H., additional, and Bajwa–ten Broeke, Sanne W., additional
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- 2023
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21. NIPTeR: an R package for fast and accurate trisomy prediction in non-invasive prenatal testing
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Johansson, Lennart F., de Weerd, Hendrik A., de Boer, Eddy N., van Dijk, Freerk, te Meerman, Gerard J., Sijmons, Rolf H., Sikkema-Raddatz, Birgit, and Swertz, Morris A.
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- 2018
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22. Investigation of Rare Non-Coding Variants in Familial Multiple Myeloma
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Niazi, Yasmeen, primary, Paramasivam, Nagarajan, additional, Blocka, Joanna, additional, Kumar, Abhishek, additional, Huhn, Stefanie, additional, Schlesner, Matthias, additional, Weinhold, Niels, additional, Sijmons, Rolf, additional, De Jong, Mirjam, additional, Durie, Brian, additional, Goldschmidt, Hartmut, additional, Hemminki, Kari, additional, and Försti, Asta, additional
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- 2022
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23. Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia
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Schubert, Stephanie A, Ruano, Dina, Elsayed, Fadwa A, Boot, Arnoud, Crobach, Stijn, Sarasqueta, Arantza Farina, Wolffenbuttel, Bruce, van der Klauw, Melanie M, Oosting, Jan, Tops, Carli M, van Eijk, Ronald, Vasen, Hans FA, Vossen, Rolf HAM, Nielsen, Maartje, Castellví-Bel, Sergi, Ruiz-Ponte, Clara, Tomlinson, Ian, Dunlop, Malcolm G, Vodicka, Pavel, Wijnen, Juul T, Hes, Frederik J, Morreau, Hans, de Miranda, Noel FCC, Sijmons, Rolf H, and van Wezel, Tom
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- 2017
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24. Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
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Dominguez-Valentin, Mev, Sampson, Julian R., Seppälä, Toni T., ten Broeke, Sanne W., Plazzer, John-Paul, Nakken, Sigve, Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Thomas, Huw, Evans, D. Gareth, Burn, John, Greenblatt, Marc, Hovig, Eivind, de Vos tot Nederveen Cappel, Wouter H., Sijmons, Rolf H., Bertario, Lucio, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Köstner, Francisco, Gluck, Nathan, Katz, Lior H., Heinimann, Karl, Vaccaro, Carlos A., Büttner, Reinhard, Görgens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, Knebel Doeberitz, Magnus von, Loeffler, Markus, Rahner, Nils, Schackert, Hans K., Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Wadt, Karin, Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Moreira, Leticia, Sánchez, Ariadna, Serra-Burriel, Miquel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Denton, Oliver G., Frayling, Ian M., Rødland, Einar Andreas, Vasen, Hans, Mints, Miriam, Neffa, Florencia, Esperon, Patricia, Alvarez, Karin, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Tjandra, Douglas, Winship, Ingrid M., Macrae, Finlay, Möslein, Gabriela, Mecklin, Jukka-Pekka, Nielsen, Maartje, and Møller, Pål
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- 2020
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25. Is HLA type a possible cancer risk modifier in Lynch syndrome?
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Ahadova, Aysel, Witt, Johannes, Haupt, Saskia, Gallon, Richard, Hueneburg, Robert, Nattermann, Jacob, Ten Broeke, Sanne, Bohaumilitzky, Lena, Hernandez-Sanchez, Alejandro, Santibanez-Koref, Mauro, Jackson, Michael S., Ahtiainen, Maarit, Pylvanainen, Kirsi, Andini, Katarina, Grolmusz, Vince Kornel, Moeslein, Gabriela, Dominguez-Valentin, Mev, Moller, Pal, Fuerst, Daniel, Sijmons, Rolf, Borthwick, Gillian M., Burn, John, Mecklin, Jukka-Pekka, Heuveline, Vincent, Doeberitz, Magnus von Knebel, Seppälä, Toni, Kloor, Matthias, Tampere University, Clinical Medicine, TAYS Cancer Centre, ATG - Applied Tumor Genomics, HUS Abdominal Center, and II kirurgian klinikka
- Subjects
HEREDITARY COLORECTAL-CANCER ,SUSCEPTIBILITY LOCI ,cancer immunoediting ,MICROSATELLITE INSTABILITY ,MUTATIONS ,immune surveillance ,CHECKPOINT BLOCKADE ,3122 Cancers ,HUMAN-LEUKOCYTE ANTIGEN ,REPEAT SEQUENCES ,personalized cancer risk ,HLA genotype ,Lynch syndrome ,IMMUNE-RESPONSE ,GENOME-WIDE ASSOCIATION ,GASTRIC-CANCER - Abstract
Lynch syndrome (LS) is the most common inherited cancer syndrome. It is inherited via a monoallelic germline variant in one of the DNA mismatch repair (MMR) genes. LS carriers have a broad 30% to 80% risk of developing various malignancies, and more precise, individual risk estimations would be of high clinical value, allowing tailored cancer prevention and surveillance. Due to MMR deficiency, LS cancers are characterized by the accumulation of frameshift mutations leading to highly immunogenic frameshift peptides (FSPs). Thus, immune surveillance is proposed to inhibit the outgrowth of MMR-deficient cell clones. Recent studies have shown that immunoediting during the evolution of MMR-deficient cancers leads to a counter-selection of highly immunogenic antigens. The immunogenicity of FSPs is dependent on the antigen presentation. One crucial factor determining antigen presentation is the HLA genotype. Hence, a LS carrier's HLA genotype plays an important role in the presentation of FSP antigens to the immune system, and may influence the likelihood of progression from precancerous lesions to cancer. To address the challenge of clarifying this possibility including diverse populations with different HLA types, we have established the INDICATE initiative (Individual cancer risk by HLA type, http://indicate-lynch.org/), an international network aiming at a systematic evaluation of the HLA genotype as a possible cancer risk modifier in LS. Here we summarize the current knowledge on the role of HLA type in cancer risk and outline future research directions to delineate possible association in the scenario of LS with genetically defined risk population and highly immunogenic tumors. publishedVersion
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- 2022
26. Feasibility of Follow-Up Studies and Reclassification in Spinocerebellar Ataxia Gene Variants of Unknown Significance
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Ghorbani, Fatemeh, primary, Alimohamed, Mohamed Z., additional, Vilacha, Juliana F., additional, Van Dijk, Krista K., additional, De Boer-Bergsma, Jelkje, additional, Fokkens, Michiel R., additional, Lemmink, Henny, additional, Sijmons, Rolf H., additional, Sikkema-Raddatz, Birgit, additional, Groves, Matthew R., additional, Verschuuren-Bemelmans, Corien C., additional, Verbeek, Dineke S., additional, Van Diemen, Cleo C., additional, and Westers, Helga, additional
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- 2022
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27. Validation of New Gene Variant Classification Methods: a Field-Test in Diagnostic Cardiogenetics
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Alimohamed, Mohamed Z., primary, Westers, Helga, additional, Vos, Yvonne J., additional, Van der Velde, K. Joeri, additional, Sijmons, Rolf H., additional, Van der Zwaag, Paul A., additional, Sikkema-Raddatz, Birgit, additional, and Jongbloed, Jan D. H., additional
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- 2022
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28. Additional file 1 of Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium
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Møller, Pål, Seppälä, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Valle, Adriana Della, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinário, Thomas, Huw, Zaránd, Attila, Mecklin, Jukka-Pekka, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomäki, Päivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hüneburg, Robert, de Vargas, Aída Falcón, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillén-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubiński, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Dębniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldés, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Verónica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Jürgen, Redler, Silke, Büttner, Reinhard, Heuveline, Vincent, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Dueñas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernán, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.
- Abstract
Additional file 1.
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- 2022
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29. Thyroid cancer in a patient with a germline MSH2 mutation. Case report and review of the Lynch syndrome expanding tumour spectrum
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Stulp Rein P, Herkert Johanna C, Karrenbeld Arend, Mol Bart, Vos Yvonne J, and Sijmons Rolf H
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Lynch syndrome ,mutations ,MSH2 ,thyroid cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract Lynch syndrome (HNPCC) is a dominantly inherited disorder characterized by germline defects in DNA mismatch repair (MMR) genes and the development of a variety of cancers, predominantly colorectal and endometrial. We present a 44-year-old woman who was shown to carry the truncating MSH2 gene mutation that had previously been identified in her family. Recently, she had been diagnosed with an undifferentiated carcinoma of the thyroid and an adenoma of her coecum. Although the thyroid carcinoma was not MSI-high (1 out of 5 microsatellites instable), it did show complete loss of immunohistochemical expression for the MSH2 protein, suggesting that this tumour was not coincidental. Although the risks for some tumour types, including breast cancer, soft tissue sarcoma and prostate cancer, are not significantly increased in Lynch syndrome, MMR deficiency in the presence of a corresponding germline defect has been demonstrated in incidental cases of a growing range of tumour types, which is reviewed in this paper. Interestingly, the MSH2-associated tumour spectrum appears to be wider than that of MLH1 and generally the risk for most extra-colonic cancers appears to be higher for MSH2 than for MLH1 mutation carriers. Together with a previously reported case, our findings show that anaplastic thyroid carcinoma can develop in the setting of Lynch syndrome. Uncommon Lynch syndrome-associated tumour types might be useful in the genetic analysis of a Lynch syndrome suspected family if samples from typical Lynch syndrome tumours are unavailable.
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- 2008
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30. Encyclopaedia of tumour-associated familial disorders. Part I: from AIMAH to CHIME syndrome
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Sijmons Rolf H
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familial cancer ,tumour syndromes ,database ,genes ,review ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract Cancer is associated with a wide range of hereditary disorders. Recognizing these disorders in cancer patients may be of great importance for the medical management of both patients and their relatives. Conversely, recognizing the fact that cancer may develop as a complication of a particular hereditary disorder which has already been diagnosed may be important for the same reason. The Familial Cancer Database (FaCD) is a web-based application http://www.facd.info which has been developed at our department with the intention to assist clinicians and genetic counsellors in making a genetic differential diagnosis in cancer patients, as well as in becoming aware of the tumour spectrum associated with hereditary disorders that have already been diagnosed in their patients. This encyclopaedia is published in parts and discusses the disorders included in the FaCD database in alphabetical order. It lists names, synonyms, OMIM number, mode of inheritance, associated genes, phenotype, clinical discussion and references. The purpose of presenting this encyclopaedia in paper format is simply that we hope that you as clinicians and researchers find it helpful to browse through it and familiarize yourself even better with the scope of genetic disorders that have been associated with increased tumour risk.
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- 2008
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31. Clinical and genetic aspects of testicular germ cell tumours
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Holzik Martijn, Sijmons Rolf H, Hoekstra-Weebers Josette EHM, Sleijfer Dirk T, and Hoekstra Harald J
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testicular germ cell tumour ,genetics ,familial ,therapy ,review ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs). TGCT is the most common type of malignant disorder in men aged 15-40 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.
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- 2008
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32. Familial Multiple Myeloma: Report on Two Families and Discussion of Screening Options
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Gerkes Erica H, de Jong Mirjam M, Sijmons Rolf H, and Vellenga Edo
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multiple myeloma ,familial ,screening ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract Multiple myeloma (MM) is a relatively rare haematological malignancy seen in older persons. It has an unknown aetiology and usually occurs incidentally within a family. However, several families have been reported with multiple cases of MM, so that the existence of hereditary MM has been postulated although no causative germline mutations have been detected so far. First-degree relatives of MM patients have been reported to have a relative risk between two and four times higher than normal of developing MM and we presume the risks are higher for relatives in the case of familial MM. Here we report on two families with MM who requested presymptomatic screening of healthy relatives. Although risk estimates for asymptomatic relatives in these types of families are not available, a clinically significant risk of developing MM cannot be excluded. We suggest that, in a research setting, screening for MM could be offered to individuals with more than one first-degree affected relative, or to those with one first-degree and at least one second-degree relative with MM. We propose a screening programme of annual protein electrophoresis of blood and urine, starting at age 40 (or earlier if a family member presented with MM at a younger age).
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- 2007
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33. Investigation of Rare Non-Coding Variants in Familial Multiple Myeloma.
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Niazi, Yasmeen, Paramasivam, Nagarajan, Blocka, Joanna, Kumar, Abhishek, Huhn, Stefanie, Schlesner, Matthias, Weinhold, Niels, Sijmons, Rolf, De Jong, Mirjam, Durie, Brian, Goldschmidt, Hartmut, Hemminki, Kari, and Försti, Asta
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MULTIPLE myeloma ,GENOME-wide association studies ,MITOGEN-activated protein kinases ,BONE marrow cells ,MONOCLONAL antibodies ,PLASMA cells ,NUCLEOTIDE sequencing - Abstract
Multiple myeloma (MM) is a plasma cell malignancy whereby a single clone of plasma cells over-propagates in the bone marrow, resulting in the increased production of monoclonal immunoglobulin. While the complex genetic architecture of MM is well characterized, much less is known about germline variants predisposing to MM. Genome-wide sequencing approaches in MM families have started to identify rare high-penetrance coding risk alleles. In addition, genome-wide association studies have discovered several common low-penetrance risk alleles, which are mainly located in the non-coding genome. Here, we further explored the genetic basis in familial MM within the non-coding genome in whole-genome sequencing data. We prioritized and characterized 150 upstream, 5′ untranslated region (UTR) and 3′ UTR variants from 14 MM families, including 20 top-scoring variants. These variants confirmed previously implicated biological pathways in MM development. Most importantly, protein network and pathway enrichment analyses also identified 10 genes involved in mitogen-activated protein kinase (MAPK) signaling pathways, which have previously been established as important MM pathways. [ABSTRACT FROM AUTHOR]
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- 2023
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34. Variation in the Risk of Colorectal Cancer for Lynch Syndrome: A retrospective family cohort study
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Win, Aung Ko, Dowty, James G., Reece, Jeanette C., Lee, Grant, Templeton, Allyson S., Plazzer, John-Paul, Buchanan, Daniel D., Akagi, Kiwamu, Aksoy, Seçil, Alonso, Angel, Alvarez, Karin, Amor, David J., Ankathil, Ravindran, Aretz, Stefan, Arnold, Julie L., Aronson, Melyssa, Austin, Rachel, Backman, Ann-Sofie, Bajwa–ten Broeke, Sanne W., Barca-Tierno, Verónica, Barwell, Julian, Bernstein, Inge, Berthet, Pascaline, Betz, Beate, Bignon, Yves-Jean, Boisjoli, Talya, Bonadona, Valérie, Briollais, Laurent, Brunet, Joan, Bucksch, Karolin, Buecher, Bruno, Buettner, Reinhard, Burn, John, Caldés, Trinidad, Capella, Gabriel, Caron, Olivier, Casey, Graham, Chew, Min H., Choi, Yun-hee, Church, James, Clendenning, Mark, Colas, Chrystelle, Cops, Elisa J., Coupier, Isabelle, Cruz-Correa, Marcia, de la Chapelle, Albert, de Wind, Niels, Dębniak, Tadeusz, Della Valle, Adriana, Delnatte, Capuccine, Dhooge, Marion, Dominguez-Valentin, Mev, Drouet, Youenn, Duijkers, Floor A., Engel, Christoph, Esperon, Patricia, Evans, D. Gareth, de Vargas, Aída Falcón, Figueiredo, Jane C, Foulkes, William, Fourme, Emmanuelle, Frebourg, Thierry, Gallinger, Steven, Garre, Pilar, Genuardi, Maurizio, Gerdes, Anne-Marie, Gima, Lauren M., Giraud, Sophie, Goodwin, Annabel, Görgens, Heike, Green, Kate, Guillem, Jose, Guillén-Ponce, Carmen, Guimbaud, Roselyne, Guindalini, Rodrigo S. C., Half, Elizabeth E., Hall, Michael J, Hampel, Heather, Hansen, Thomas V. O., Heinimann, Karl, Hes, Frederik J., Hill, James, Ho, Judy W.C., Holinski-Feder, Elke, Hoogerbrugge, Nicoline, Hüneburg, Robert, Huntley, Vanessa, James, Paul A., Jensen, Uffe B, John, Thomas, Juhari, Wan K.W., Kalady, Matthew, Kastrinos, Fay, Kloor, Matthias, Kohonen-Corish, Maija RJ, Krogh, Lotte N., Kupfer, Sonia S., Ladabaum, Uri, Lagerstedt-Robinson, Kristina, Lalloo, Fiona, Lasset, Christine, Latchford, Andrew, Laurent-Puig, Pierre, Lautrup, Charlotte K., Leggett, Barbara A., Lejeune, Sophie, LeMarchand, Loic, Ligtenberg, Marjolijn, Lindor, Noralane, Loeffler, Markus, Longy, Michel, Lopez, Francisco, Lowery, Jan, Lubiński, Jan, Lucassen, Anneke M, Lynch, Patrick M., Malińska, Karolina, Matsubara, Nagahide, Mecklin, Jukka-Pekka, Møller, Pål, Monahan, Kevin, Morrison, Patrick J., Nattermann, Jacob, Navarro, Matilde, Neffa, Florencia, Neklason, Deborah, Newcomb, Polly A., Ngeow, Joanne, Nichols, Cassandra, Nielsen, Maartje, Nixon, Dawn M., Nogues, Catherine, Okkels, Henrik, Olschwang, Sylviane, Pachter, Nicholas, Pai, Rish K., Palmero, Edenir I., Pande, Mala, Parry, Susan, Patel, Swati G., Pearlman, Rachel, Perne, Claudia, Pineda, Marta, Poplawski, Nicola K, Pylvänäinen, Kirsi, Qiu, Jay, Rahner, Nils, Ramesar, Raj, Rasmussen, Lene J., Redler, Silke, Reis, Rui M., Ricciardiello, Luigi, Rogoża-Janiszewska, Emilia, Rosty, Christophe, Samadder, N. Jewel, Sampson, Julian R., Schackert, Hans K., Schmiegel, Wolff, Schulmann, Karsten, Schuster, Helène, Scott, Rodney, Senter, Leigha, Seppälä, Toni T, Shtoyerman, Rakefet, Sijmons, Rolf H., Snyder, Carrie, Solomon, Ilana B., Soto, Jose Luis, Southey, Melissa C., Spigelman, Allan, Spirandelli, Florencia, Spurdle, Amanda B., Steinke-Lange, Verena, Stoffel, Elena M., Strassburg, Christian P., Sunde, Lone, Susman, Rachel, Syngal, Sapna, Tanakaya, Kohji, Tezcan, Gülçin, Therkildsen, Christina, Thibodeau, Steve, Tomita, Naohiro, Tucker, Katherine M., Tunca, Berrin, Turchetti, Daniela, Uhrhammer, Nancy, Utsunomiya, Joji, Vaccaro, Carlos, van Duijnhoven, Fränzel J.B., van Wanzeele, Meghan J., Vangala, Deepak B., Vasen, Hans F.A., von Knebel Doeberitz, Magnus, von Salomé, Jenny, Wadt, Karin A. W., Ward, Robyn L., Weitz, Jürgen, Weitzel, Jeffrey N., Williams, Heinric, Winship, Ingrid, Wise, Paul E., Wods, Julie, Woods, Michael O., Yamaguchi, Tatsuro, Zachariae, Silke, Zahary, Mohd N., Hopper, John L., Haile, Robert W., Macrae, Finlay A., Möslein, Gabriela, and Jenkins, Mark A.
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Article - Abstract
BACKGROUND: Current clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the average age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate how much penetrance varies between carriers of pathogenic variants in the same gene by sex and continent of residence of the carrier. METHODS: We studied 79,809 relatives from 5,255 families, of at least three relatives, in which at least one was a confirmed carrier of a pathogenic or likely pathogenic variant in a mismatch repair gene (1,829 MLH1, 2,179 MSH2, 798 MSH6, 449 PMS2), recruited in 15 countries from North America, Europe and Australasia by the collaborative centres of the International Mismatch Repair Consortium. We used modified segregation analysis conditioned on ascertainment to estimate the average penetrance and modelled unmeasured polygenic factors to estimate the variation in penetrance of colorectal cancer. The existence of familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested using a Wald p-value for the null hypothesis that the polygenic standard deviation is zero. FINDINGS: There was strong evidence of the existence of familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was more prominent for MLH1 and MSH2 variant carriers; depending on gene, sex, and continent, with 7–56% of carriers having a risk of colorectal cancer to age 80 of less than 20%, and 9–44% having a risk of more than 80%, while only 10–19% had a risk of 40–60%. INTERPRETATION: Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessment for precision prevention and early detection of colorectal cancer for Lynch syndrome.
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- 2021
35. Familial Cervical Cancer: Case Reports, Review and Clinical Implications
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Zoodsma Margreet, Sijmons Rolf H, de Vries Elisabeth GE, and Zee Ate
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cervical cancer ,familial ,family history ,risk ,screening ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract We report three Dutch families with familial clustering of (pre)neoplastic cervical disease, review the literature on familial risks of cervical intraepithelial neoplasia (CIN) and cervical cancer, and discuss possible practical guidelines for women with a family history of cervical cancer. Daughters and sisters of women with cervical cancer have been reported to have a relative risk of 1.5-2.3 to develop this type of cancer. From a practical clinical point of view, we suggest that as in women with an increased non-genetic risk to develop cervical cancer (e.g. because of immunosuppressive therapy) increased surveillance to detect this tumour should be considered in women with an increased risk based on family history. Cessation of smoking should be advised. As the use of condoms at least prevents HPV re-infection its use can be recommended as a way to lower the cervical cancer risk. Future studies to determine the genetic contribution to the development of cervical cancer should include the paternal family history of cancer and, because genetic predisposition might express itself as a higher risk to develop precursors of cervical cancer, carcinoma in situ and CIN grade II-III.
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- 2004
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36. Erratum: Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia
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Schubert, Stephanie A, Ruano, Dina, Elsayed, Fadwa A, Boot, Arnoud, Crobach, Stijn, Sarasqueta, Arantza Farina, Wolffenbuttel, Bruce, van der Klauw, Melanie M, Oosting, Jan, Tops, Carli M, van Eijk, Ronald, Vasen, Hans FA, Vossen, Rolf HAM, Nielsen, Maartje, Castellví-Bel, Sergi, Ruiz-Ponte, Clara, Tomlinson, Ian, Dunlop, Malcolm G, Vodicka, Pavel, Wijnen, Juul T, Hes, Frederik J, Morreau, Hans, de Miranda, Noel FCC, Sijmons, Rolf H, and van Wezel, Tom
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- 2018
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37. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
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Dominguez-Valentin, Mev, primary, Plazzer, John-Paul, additional, Sampson, Julian R., additional, Engel, Christoph, additional, Aretz, Stefan, additional, Jenkins, Mark A., additional, Sunde, Lone, additional, Bernstein, Inge, additional, Capella, Gabriel, additional, Balaguer, Francesc, additional, Macrae, Finlay, additional, Winship, Ingrid M., additional, Thomas, Huw, additional, Evans, Dafydd Gareth, additional, Burn, John, additional, Greenblatt, Marc, additional, de Vos tot Nederveen Cappel, Wouter H., additional, Sijmons, Rolf H., additional, Nielsen, Maartje, additional, Bertario, Lucio, additional, Bonanni, Bernardo, additional, Tibiletti, Maria Grazia, additional, Cavestro, Giulia Martina, additional, Lindblom, Annika, additional, Valle, Adriana Della, additional, Lopez-Kostner, Francisco, additional, Alvarez, Karin, additional, Gluck, Nathan, additional, Katz, Lior, additional, Heinimann, Karl, additional, Vaccaro, Carlos A., additional, Nakken, Sigve, additional, Hovig, Eivind, additional, Green, Kate, additional, Lalloo, Fiona, additional, Hill, James, additional, Vasen, Hans F. A., additional, Perne, Claudia, additional, Büttner, Reinhard, additional, Görgens, Heike, additional, Holinski-Feder, Elke, additional, Morak, Monika, additional, Holzapfel, Stefanie, additional, Hüneburg, Robert, additional, von Knebel Doeberitz, Magnus, additional, Loeffler, Markus, additional, Rahner, Nils, additional, Weitz, Jürgen, additional, Steinke-Lange, Verena, additional, Schmiegel, Wolff, additional, Vangala, Deepak, additional, Crosbie, Emma J., additional, Pineda, Marta, additional, Navarro, Matilde, additional, Brunet, Joan, additional, Moreira, Leticia, additional, Sánchez, Ariadna, additional, Serra-Burriel, Miquel, additional, Mints, Miriam, additional, Kariv, Revital, additional, Rosner, Guy, additional, Piñero, Tamara Alejandra, additional, Pavicic, Walter Hernán, additional, Kalfayan, Pablo, additional, Broeke, Sanne W. ten, additional, Mecklin, Jukka-Pekka, additional, Pylvänäinen, Kirsi, additional, Renkonen-Sinisalo, Laura, additional, Lepistö, Anna, additional, Peltomäki, Päivi, additional, Hopper, John L., additional, Win, Aung Ko, additional, Buchanan, Daniel D., additional, Lindor, Noralane M., additional, Gallinger, Steven, additional, Marchand, Loïc Le, additional, Newcomb, Polly A., additional, Figueiredo, Jane C., additional, Thibodeau, Stephen N., additional, Therkildsen, Christina, additional, Hansen, Thomas V. O., additional, Lindberg, Lars, additional, Rødland, Einar Andreas, additional, Neffa, Florencia, additional, Esperon, Patricia, additional, Tjandra, Douglas, additional, Möslein, Gabriela, additional, Seppälä, Toni T., additional, and Møller, Pål, additional
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- 2021
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38. Additional file 1 of A rare large duplication of MLH1 identified in Lynch syndrome
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Abhishek Kumar, Nagarajan Paramasivam, Obul Reddy Bandapalli, Schlesner, Matthias, Tianhui Chen, Sijmons, Rolf, Dymerska, Dagmara, Golebiewska, Katarzyna, Kuswik, Magdalena, Lubinski, Jan, Hemminki, Kari, and Försti, Asta
- Abstract
Additional file 1: Fig. S1. (Family B) Pedigree of the colorectal cancer family with MLH1 frameshift variant. (Family C) Pedigree of the colorectal cancer family with MSH2 splice site variant. Fig. S2. Microsatellite instability (MSI) analysis of the tumor samples of two family members from Family A and one tumor sample from Family C. For each family, individuals with the tumor samples analyzed are indicated by an arrow and the MSI plots are shown for the corresponding germline and tumor samples. Table S1. Number of large deletions and duplications in the mismatch repair genes reported in the InSiGHT database and their clinical classification according to Mismatch Repair Gene Variant Classification Criteria by the InSiGHT Variant Interpretation Committee.
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- 2021
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39. Uptake of hysterectomy and bilateral salpingooophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report
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Seppala, Toni T., Dominguez-Valentin, Mev, Crosbie, Emma J., Engel, Christoph, Aretz, Stefan, Macrae, Finlay, Winship, Ingrid, Capella, Gabriel, Thomas, Huw, Hovig, Eivind, Nielsen, Maartje, Sijmons, Rolf H., Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria G., Cavestro, Giulia M., Mints, Miriam, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Green, Kate, Lalloo, Fiona, Hill, James, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Strauss, Hans-Georg, Tecklenburg, Johanna, Holinski-Feder, Elke, Steinke-Lange, Verena, Mecklin, Jukka-Pekka, Plazzer, John-Paul, Pineda, Marta, Navarro, Matilde, Vida, Joan B., Kariv, Revital, Rosner, Guy, Pinero, Tamara A., Pavicic, Walter, Kalfayan, Pablo, Ten Broeke, Sanne W., Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Burn, John, Greenblatt, Marc, Cappel, Wouter H. de Vos Tot Nederveen, Della Valle, Adriana, Lopez-Koestner, Francisco, Alvarez, Karin, Buettner, Reinhard, Goergens, Heike, Morak, Monika, Holzapfel, Stefanie, Hueneburg, Robert, Doeberitz, Magnus von Knebel, Loeffler, Markus, Redler, Silke, Weitz, Jurgen, Pylvaenaeinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Hopper, John L., Win, Aung K., Lindor, Noralane M., Gallinger, Steven, Marchand, Loic Le, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Wadt, Karin A. W., Mourits, Marian J. E., Ketabi, Zohreh, Denton, Oliver G., Rodland, Einar A., Vasen, Hans, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Moeslein, Gabriela, Rokkones, Erik, Sampson, Julian R., Evans, D. G., Moller, Pal, Seppala, Toni T., Dominguez-Valentin, Mev, Crosbie, Emma J., Engel, Christoph, Aretz, Stefan, Macrae, Finlay, Winship, Ingrid, Capella, Gabriel, Thomas, Huw, Hovig, Eivind, Nielsen, Maartje, Sijmons, Rolf H., Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria G., Cavestro, Giulia M., Mints, Miriam, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Green, Kate, Lalloo, Fiona, Hill, James, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Strauss, Hans-Georg, Tecklenburg, Johanna, Holinski-Feder, Elke, Steinke-Lange, Verena, Mecklin, Jukka-Pekka, Plazzer, John-Paul, Pineda, Marta, Navarro, Matilde, Vida, Joan B., Kariv, Revital, Rosner, Guy, Pinero, Tamara A., Pavicic, Walter, Kalfayan, Pablo, Ten Broeke, Sanne W., Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Burn, John, Greenblatt, Marc, Cappel, Wouter H. de Vos Tot Nederveen, Della Valle, Adriana, Lopez-Koestner, Francisco, Alvarez, Karin, Buettner, Reinhard, Goergens, Heike, Morak, Monika, Holzapfel, Stefanie, Hueneburg, Robert, Doeberitz, Magnus von Knebel, Loeffler, Markus, Redler, Silke, Weitz, Jurgen, Pylvaenaeinen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Hopper, John L., Win, Aung K., Lindor, Noralane M., Gallinger, Steven, Marchand, Loic Le, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Wadt, Karin A. W., Mourits, Marian J. E., Ketabi, Zohreh, Denton, Oliver G., Rodland, Einar A., Vasen, Hans, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Moeslein, Gabriela, Rokkones, Erik, Sampson, Julian R., Evans, D. G., and Moller, Pal
- 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 syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd.
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- 2021
40. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
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Dominguez-Valentin, Mev, Plazzer, John-Paul, Sampson, Julian R., Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Macrae, Finlay, Winship, Ingrid M., Thomas, Huw, Evans, Dafydd Gareth, Burn, John, Greenblatt, Marc, Cappel, Wouter H. de Vos Tot Nederveen, Sijmons, Rolf H., Nielsen, Maartje, Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Kostner, Francisco, Alvarez, Karin, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Nakken, Sigve, Hovig, Eivind, Green, Kate, Lalloo, Fiona, Hill, James, Vasen, Hans F. A., Perne, Claudia, Buettner, Reinhard, Goergens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hueneburg, Robert, Doeberitz, Magnus von Knebel, Loeffler, Markus, Rahner, Nils, Weitz, Juergen, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Crosbie, Emma J., Pineda, Marta, Navarro, Matilde, Brunet, Joan, Moreira, Leticia, Sanchez, Ariadna, Serra-Burriel, Miquel, Mints, Miriam, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Pavicic, Walter Hernan, Kalfayan, Pablo, ten Broeke, Sanne W., Mecklin, Jukka-Pekka, Pylvanainen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomaki, Paivi, Hopper, John L., Win, Aung Ko, Buchanan, Daniel D., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loic, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Hansen, Thomas V. O., Lindberg, Lars, Rodland, Einar Andreas, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Moslein, Gabriela, Seppala, Toni T., Moller, Pal, Dominguez-Valentin, Mev, Plazzer, John-Paul, Sampson, Julian R., Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Macrae, Finlay, Winship, Ingrid M., Thomas, Huw, Evans, Dafydd Gareth, Burn, John, Greenblatt, Marc, Cappel, Wouter H. de Vos Tot Nederveen, Sijmons, Rolf H., Nielsen, Maartje, Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Kostner, Francisco, Alvarez, Karin, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Nakken, Sigve, Hovig, Eivind, Green, Kate, Lalloo, Fiona, Hill, James, Vasen, Hans F. A., Perne, Claudia, Buettner, Reinhard, Goergens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hueneburg, Robert, Doeberitz, Magnus von Knebel, Loeffler, Markus, Rahner, Nils, Weitz, Juergen, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Crosbie, Emma J., Pineda, Marta, Navarro, Matilde, Brunet, Joan, Moreira, Leticia, Sanchez, Ariadna, Serra-Burriel, Miquel, Mints, Miriam, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Pavicic, Walter Hernan, Kalfayan, Pablo, ten Broeke, Sanne W., Mecklin, Jukka-Pekka, Pylvanainen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomaki, Paivi, Hopper, John L., Win, Aung Ko, Buchanan, Daniel D., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loic, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Hansen, Thomas V. O., Lindberg, Lars, Rodland, Einar Andreas, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Moslein, Gabriela, Seppala, Toni T., and Moller, Pal
- 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.
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- 2021
41. Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants:a Prospective Lynch Syndrome Database report
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Seppälä, Toni T., Dominguez-Valentin, Mev, Crosbie, Emma J., Engel, Christoph, Aretz, Stefan, Macrae, Finlay, Winship, Ingrid, Capella, Gabriel, Thomas, Huw, Hovig, Eivind, Nielsen, Maartje, Sijmons, Rolf H., Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria G., Cavestro, Giulia M., Mints, Miriam, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Green, Kate, Lalloo, Fiona, Hill, James, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Strauß, Hans Georg, Tecklenburg, Johanna, Holinski-Feder, Elke, Steinke-Lange, Verena, Mecklin, Jukka Pekka, Plazzer, John Paul, Pineda, Marta, Navarro, Matilde, Vida, Joan B., Kariv, Revital, Rosner, Guy, Piñero, Tamara A., Pavicic, Walter, Kalfayan, Pablo, ten Broeke, Sanne W., Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Burn, John, Greenblatt, Marc, de Vos tot Nederveen Cappel, Wouter H., Della Valle, Adriana, Lopez-Koestner, Francisco, Alvarez, Karin, Büttner, Reinhard, Görgens, Heike, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, von Knebel Doeberitz, Magnus, Loeffler, Markus, Redler, Silke, Weitz, Jürgen, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Hopper, John L., Win, Aung K., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Wadt, Karin A.W., Mourits, Marian J.E., Ketabi, Zohreh, Denton, Oliver G., Rødland, Einar A., Vasen, Hans, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Möslein, Gabriela, Rokkones, Erik, Sampson, Julian R., Evans, D. G., Møller, Pål, Seppälä, Toni T., Dominguez-Valentin, Mev, Crosbie, Emma J., Engel, Christoph, Aretz, Stefan, Macrae, Finlay, Winship, Ingrid, Capella, Gabriel, Thomas, Huw, Hovig, Eivind, Nielsen, Maartje, Sijmons, Rolf H., Bertario, Lucio, Bonanni, Bernardo, Tibiletti, Maria G., Cavestro, Giulia M., Mints, Miriam, Gluck, Nathan, Katz, Lior, Heinimann, Karl, Vaccaro, Carlos A., Green, Kate, Lalloo, Fiona, Hill, James, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Strauß, Hans Georg, Tecklenburg, Johanna, Holinski-Feder, Elke, Steinke-Lange, Verena, Mecklin, Jukka Pekka, Plazzer, John Paul, Pineda, Marta, Navarro, Matilde, Vida, Joan B., Kariv, Revital, Rosner, Guy, Piñero, Tamara A., Pavicic, Walter, Kalfayan, Pablo, ten Broeke, Sanne W., Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Burn, John, Greenblatt, Marc, de Vos tot Nederveen Cappel, Wouter H., Della Valle, Adriana, Lopez-Koestner, Francisco, Alvarez, Karin, Büttner, Reinhard, Görgens, Heike, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, von Knebel Doeberitz, Magnus, Loeffler, Markus, Redler, Silke, Weitz, Jürgen, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Lepistö, Anna, Hopper, John L., Win, Aung K., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Therkildsen, Christina, Wadt, Karin A.W., Mourits, Marian J.E., Ketabi, Zohreh, Denton, Oliver G., Rødland, Einar A., Vasen, Hans, Neffa, Florencia, Esperon, Patricia, Tjandra, Douglas, Möslein, Gabriela, Rokkones, Erik, Sampson, Julian R., Evans, D. G., and Møller, Pål
- 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
42. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis
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Hes, Frederik J, Ruano, Dina, Nieuwenhuis, Marry, Tops, Carli M, Schrumpf, Melanie, Nielsen, Maartje, Huijts, Petra E A, Wijnen, Juul T, Wagner, Anja, García, Encarna B Gómez, Sijmons, Rolf H, Menko, Fred H, Letteboer, Tom G W, Hoogerbrugge, Nicoline, Harryvan, Jan, Kampman, Ellen, Morreau, Hans, Vasen, Hans F A, and van Wezel, Tom
- Published
- 2014
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43. The Use of a Diagnostic Database in Clinical Oncogenetics
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Sijmons Rolf H and Burger Gerard TN
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hereditary cancer ,familial cancer ,differential diagnosis ,database ,software ,computer-assisted diagnosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract In addition to a relatively small number of well known hereditary cancer syndromes, hundreds of presumed or proven hereditary disorders have been observed to manifest cancer as a characteristic feature or as a possible complication. The recognition of these disorders may be of great importance for the medical management of the families involved. Specialized databases, like the Familial Cancer Database (FaCD, http://www.facd.info), may be helpful in the making of differential diagnoses and offer advantages compared with traditional textbooks and on-line literature searches. Based on our own experience and interviews with the other Dutch family cancer clinics, we expect that in similar clinics, computer-assisted differential diagnosis will be primarily used in helping to decide whether or not cancer patients and families should be referred to family cancer clinics for further study and counseling. FaCD has been developed as a tool for experts. As general practitioners and other health professionals with non-expert knowledge of cancer genetics are under increasing pressure to advise on genetic risks, it should be encouraged that other software is developed to support them in interpreting family histories of cancer.
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- 2003
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44. FAIR Genomes: Standardizing a meta-data schema for FAIRifying personal genome data workflows
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Singh, Gurnoor, Velde, Joeri van der, Beliën, Jeroen, Böhmer, Jasmin, Stemkens, Daphne, Vissers, Lisenka, Reeuwijk, Jeroen van, Hiltemann, Saskia, Johansson, Lennart F., Stoep, Nienke van der, Sie, Daoud, Weiss, Janneke, Frederix, Geert, Roos, Marco, Iperen, Erik van, Vrijenhoek, Terry, Asselbergs, Folkert W., Montfrans, Joris van, Sijmons, Rolf, Deutekom, Hanneke van, Neerincx, Pieter, Andrade, Fernanda de, Niehues, Anna, Kerstens, Hindrik H.D., Thompson, Mark, Kaliyaperumal, Rajaram, Jacobsen, Annika, Wolstencroft, Katy, Nijman, Ies, Nelen, Marcel, Siezen, Ariaan, Hove, Koen ten, Knoers, Nine, Gilissen, Christian, Scheffer, Hans, Willems, Stefan, Zelst-Stams, Wendy van, Ijntema, Helger, Elsink, Kim, Koning, Bart de, Ylstra, Bauke, Sistermans, Erik, Kemmeren, Patrick, Holstege, Henne, Staiger, Christine, Tops, Bastiaan, Rebers, Susanne, Zessen, David van, Retèl, Valesca, Cuppen, Edwin, Tintelen, Peter van, Enckevort, David van, Steeghs, Lieneke, Scholtens, Salome, Laros, Jeroen, Mei, Leon, Oosterwijk, Cor, Stubbs, Andrew, Hoen, Peter A.C. 't, Gijn, Mariëlle van, and Swertz, Morris
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data sharing ,meta-data ,genomics ,healthcare ,fair data principles - Abstract
The increase in personal genome data generated in diagnostics and research holds great promise for advancing personalized prevention and medicine. However, valuable genomic and associated clinical data is fragmented across many healthcare providers and research organizations, making it difficult to reuse due to lack of findability, accessibility and interoperability. This prohibits us from exploiting the potential information contained in these genomes for health benefit. FAIR Genomes aims to provide guidelines that should increase reuse of genomic data while considering the needs of all stakeholders and addressing ELSI issues. We present a standardized meta-data schema to harmonize genomic data workflows and their reporting practices. This schema is broadly segmented into five categories: general information; informed consent; personal and clinical information; material information and technical information. In face-to-face and videoconference meetings, we work towards defining the schema, which is a list of common and optional data elements with relationships and values mapped to existing ontologies such as SNOMED, DUO, HPO, UMLS and EDAM. This project aims to make all data and meta-data elements findable and interoperable to increase FAIRness and standardization in capturing genomic data. This meta-data schema provides a strong basis for digital twin data in Dutch hospitals, development of personal genetic lockers, and active Dutch participation in the European '1+ Million Genomes' Initiative. The scope of this schema goes beyond to next-generation DNA sequencing data. We expect to expand into various *omics varieties, as well as capturing analysis pipelines in FAIR terms. Hence, the FAIR Genomes meta-data framework could be used to develop other research-based infrastructures such as X-omics, BBMRI, ELIXIR, Solve-RD and European Joint Programme on Rare Diseases. The FAIR Genomes meetings are open to receive input from anyone to achieve the highest quality and usability of the resulting meta-data framework. Join us at: https://github.com/fairgenomes.  
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- 2020
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45. MUTYH and the mismatch repair system: partners in crime?
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Niessen, Renée C., Sijmons, Rolf H., Ou, J., Olthof, Sandra G. M., Osinga, Jan, Ligtenberg, Marjolijn J., Hogervorst, Frans B. L., Weiss, Marjan M., Tops, Carli M. J., Hes, Frederik J., de Bock, Geertruida H., Buys, Charles H. C. M., Kleibeuker, Jan H., and Hofstra, Robert M. W.
- Published
- 2006
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46. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants:findings from the Prospective Lynch Syndrome Database
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Dominguez-Valentin, Mev, Sampson, Julian R., Seppälä, Toni T., ten Broeke, Sanne W., Plazzer, John Paul, Nakken, Sigve, Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Thomas, Huw, Evans, D. Gareth, Burn, John, Greenblatt, Marc, Hovig, Eivind, de Vos tot Nederveen Cappel, Wouter H., Sijmons, Rolf H., Bertario, Lucio, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Köstner, Francisco, Gluck, Nathan, Katz, Lior H., Heinimann, Karl, Vaccaro, Carlos A., Büttner, Reinhard, Görgens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, Knebel Doeberitz, Magnus von, Loeffler, Markus, Rahner, Nils, Schackert, Hans K., Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Wadt, Karin, Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Moreira, Leticia, Sánchez, Ariadna, Serra-Burriel, Miquel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Denton, Oliver G., Frayling, Ian M., Rødland, Einar Andreas, Vasen, Hans, Mints, Miriam, Neffa, Florencia, Esperon, Patricia, Alvarez, Karin, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Tjandra, Douglas, Winship, Ingrid M., Macrae, Finlay, Möslein, Gabriela, Mecklin, Jukka Pekka, Nielsen, Maartje, Møller, Pål, Dominguez-Valentin, Mev, Sampson, Julian R., Seppälä, Toni T., ten Broeke, Sanne W., Plazzer, John Paul, Nakken, Sigve, Engel, Christoph, Aretz, Stefan, Jenkins, Mark A., Sunde, Lone, Bernstein, Inge, Capella, Gabriel, Balaguer, Francesc, Thomas, Huw, Evans, D. Gareth, Burn, John, Greenblatt, Marc, Hovig, Eivind, de Vos tot Nederveen Cappel, Wouter H., Sijmons, Rolf H., Bertario, Lucio, Tibiletti, Maria Grazia, Cavestro, Giulia Martina, Lindblom, Annika, Della Valle, Adriana, Lopez-Köstner, Francisco, Gluck, Nathan, Katz, Lior H., Heinimann, Karl, Vaccaro, Carlos A., Büttner, Reinhard, Görgens, Heike, Holinski-Feder, Elke, Morak, Monika, Holzapfel, Stefanie, Hüneburg, Robert, Knebel Doeberitz, Magnus von, Loeffler, Markus, Rahner, Nils, Schackert, Hans K., Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Pylvänäinen, Kirsi, Renkonen-Sinisalo, Laura, Hopper, John L., Win, Aung Ko, Haile, Robert W., Lindor, Noralane M., Gallinger, Steven, Le Marchand, Loïc, Newcomb, Polly A., Figueiredo, Jane C., Thibodeau, Stephen N., Wadt, Karin, Therkildsen, Christina, Okkels, Henrik, Ketabi, Zohreh, Moreira, Leticia, Sánchez, Ariadna, Serra-Burriel, Miquel, Pineda, Marta, Navarro, Matilde, Blanco, Ignacio, Green, Kate, Lalloo, Fiona, Crosbie, Emma J., Hill, James, Denton, Oliver G., Frayling, Ian M., Rødland, Einar Andreas, Vasen, Hans, Mints, Miriam, Neffa, Florencia, Esperon, Patricia, Alvarez, Karin, Kariv, Revital, Rosner, Guy, Pinero, Tamara Alejandra, Gonzalez, María Laura, Kalfayan, Pablo, Tjandra, Douglas, Winship, Ingrid M., Macrae, Finlay, Möslein, Gabriela, Mecklin, Jukka Pekka, Nielsen, Maartje, and Møller, Pål
- 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
47. B Cells as Prognostic Biomarker After Surgery for Colorectal Liver Metastases
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Hof, Joost, Visser, Lydia, Höppener, Diederik J, Nierop, Pieter M H, Terpstra, Miente M, Gouw, Annette S H, Grünhagen, Dirk J, Verhoef, Cornelis, Sijmons, Rolf H, de Jong, Koert P, Kok, Klaas, Hof, Joost, Visser, Lydia, Höppener, Diederik J, Nierop, Pieter M H, Terpstra, Miente M, Gouw, Annette S H, Grünhagen, Dirk J, Verhoef, Cornelis, Sijmons, Rolf H, de Jong, Koert P, and Kok, Klaas
- Abstract
Background: The aim of this study was to identify more accurate variables to improve prognostication of individual patients with colorectal liver metastases (CRLM). Clinicopathological characteristics only partly explain the large range in survival rates. Methods: MessengerRNA expression profiles of resected CRLM of two patient groups were analysed by mRNA sequencing: poor survivors (death from recurrent disease <30 months after surgery) and good survivors (no recurrent disease >60 months after surgery). Tumour and adjacent liver parenchyma samples were analysed. Results: MessengerRNA expression profiling of the tumour samples identified 77 genes that were differentially expressed between the two survival groups at a False Discovery Rate (FDR) <0.1. In the adjacent liver parenchyma samples only one gene, MTRNR2L1, showed significantly higher expression in the good survivors. Pathway analysis showed higher expression of immune-related and stroma-related genes in tumour samples from good survivors. Expression data was then validated by immunohistochemistry in two cohorts comprising a total of 125 patients. Immunohistochemical markers that showed to be associated with good survival in the total cohort were: high K/L+ infiltration in tumour stroma [p = 0.029; OR 2.500 (95% CI 1.100-5.682)] and high CD79A+ infiltration in tumour stroma [p = 0.036; OR 2.428 (95%CI 1.062-5.552)]. Conclusions: A high stromal infiltration of CD79A+ B cells and K/L+ plasma cells might be favourable prognostic biomarkers after surgery for CRLM.
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- 2020
48. InSiGHT leads in the implementation of the Human Variome Project
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Macrae Finlay, Moslein Gabriela, Cotton Richard, Sijmons Rolf, den Dunnen Johan, Woods Michael, Tavtigian Sean, Jenkins Mark, Hofstra Robert, and Haile Robert
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Published
- 2011
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49. BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes
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Domingo, Enric, Niessen, Renée C, Oliveira, Carla, Alhopuro, Pia, Moutinho, Catia, Espín, Eloi, Armengol, Manel, Sijmons, Rolf H, Kleibeuker, Jan H, Seruca, Raquel, Aaltonen, Lauri A, Imai, Kohzoh, Yamamoto, Hiroyuki, Schwartz, Jr, Simó, and Hofstra, Robert M W
- Published
- 2005
- Full Text
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50. Practical Barriers and Facilitators Experienced by Patients, Pharmacists and Physicians to the Implementation of Pharmacogenomic Screening in Dutch Outpatient Hospital Care—An Explorative Pilot Study
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Lanting, Pauline, primary, Drenth, Evelien, additional, Boven, Ludolf, additional, van Hoek, Amanda, additional, Hijlkema, Annemiek, additional, Poot, Ellen, additional, van der Vries, Gerben, additional, Schoevers, Robert, additional, Horwitz, Ernst, additional, Gans, Reinold, additional, Kosterink, Jos, additional, Plantinga, Mirjam, additional, van Langen, Irene, additional, Ranchor, Adelita, additional, Wijmenga, Cisca, additional, Franke, Lude, additional, Wilffert, Bob, additional, and Sijmons, Rolf, additional
- Published
- 2020
- Full Text
- View/download PDF
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