Author: "Mensenkamp A." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Mensenkamp A."' showing total 953 results

Start Over Author "Mensenkamp A."

953 results on '"Mensenkamp A."'

1. Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel

Author: Parsons, Michael T, de la Hoya, Miguel, Richardson, Marcy E, Tudini, Emma, Anderson, Michael, Berkofsky-Fessler, Windy, Caputo, Sandrine M, Chan, Raymond C, Cline, Melissa S, Feng, Bing-Jian, Fortuno, Cristina, Gomez-Garcia, Encarna, Hadler, Johanna, Hiraki, Susan, Holdren, Megan, Houdayer, Claude, Hruska, Kathleen, James, Paul, Karam, Rachid, Leong, Huei San, Martins, Alexandra, Mensenkamp, Arjen R, Monteiro, Alvaro N, Nathan, Vaishnavi, O'Connor, Robert, Pedersen, Inge Sokilde, Pesaran, Tina, Radice, Paolo, Schmidt, Gunnar, Southey, Melissa, Tavtigian, Sean, Thompson, Bryony A, Toland, Amanda E, Turnbull, Clare, Vogel, Maartje J, Weyandt, Jamie, Wiggins, George AR, Zec, Lauren, Couch, Fergus J, Walker, Logan C, Vreeswijk, Maaike PG, Goldgar, David E, and Spurdle, Amanda B
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Women's Health, Breast Cancer, Ovarian Cancer, Cancer, Rare Diseases, Good Health and Well Being, ACMG/AMP variant curation guidelines, BRCA1, BRCA2, ClinGen, ClinVar, VCEP, Humans, BRCA2 Protein, BRCA1 Protein, Female, Genetic Variation, Breast Neoplasms, Genomics, Databases, Genetic, Ovarian Neoplasms, Genetic Predisposition to Disease, Genetic Testing, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: The ENIGMA research consortium develops and applies methods to determine clinical significance of variants in hereditary breast and ovarian cancer genes. An ENIGMA BRCA1/2 classification sub-group, formed in 2015 as a ClinGen external expert panel, evolved into a ClinGen internal Variant Curation Expert Panel (VCEP) to align with Food and Drug Administration recognized processes for ClinVar contributions. The VCEP reviewed American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) classification criteria for relevance to interpreting BRCA1 and BRCA2 variants. Statistical methods were used to calibrate evidence strength for different data types. Pilot specifications were tested on 40 variants and documentation revised for clarity and ease of use. The original criterion descriptions for 13 evidence codes were considered non-applicable or overlapping with other criteria. Scenario of use was extended or re-purposed for eight codes. Extensive analysis and/or data review informed specification descriptions and weights for all codes. Specifications were applied to pilot variants with pre-existing ClinVar classification as follows: 13 uncertain significance or conflicting, 14 pathogenic and/or likely pathogenic, and 13 benign and/or likely benign. Review resolved classification for 11/13 uncertain significance or conflicting variants and retained or improved confidence in classification for the remaining variants. Alignment of pre-existing ENIGMA research classification processes with ACMG/AMP classification guidelines highlighted several gaps in the research processes and the baseline ACMG/AMP criteria. Calibration of evidence strength was key to justify utility and strength of different data types for gene-specific application. The gene-specific criteria demonstrated value for improving ACMG/AMP-aligned classification of BRCA1 and BRCA2 variants.
Published: 2024

2. Germline variant affecting p53β isoforms predisposes to familial cancer

Author: Schubert, Stephanie A., Ruano, Dina, Joruiz, Sebastien M., Stroosma, Jordy, Glavak, Nikolina, Montali, Anna, Pinto, Lia M., Rodríguez-Girondo, Mar, Barge-Schaapveld, Daniela Q. C. M., Nielsen, Maartje, van Nesselrooij, Bernadette P. M., Mensenkamp, Arjen R., van Leerdam, Monique E., Sharp, Thomas H., Morreau, Hans, Bourdon, Jean-Christophe, de Miranda, Noel F. C. C., and van Wezel, Tom
Published: 2024
Full Text: View/download PDF

3. Germline variant affecting p53β isoforms predisposes to familial cancer

Author: Stephanie A. Schubert, Dina Ruano, Sebastien M. Joruiz, Jordy Stroosma, Nikolina Glavak, Anna Montali, Lia M. Pinto, Mar Rodríguez-Girondo, Daniela Q. C. M. Barge-Schaapveld, Maartje Nielsen, Bernadette P. M. van Nesselrooij, Arjen R. Mensenkamp, Monique E. van Leerdam, Thomas H. Sharp, Hans Morreau, Jean-Christophe Bourdon, Noel F. C. C. de Miranda, and Tom van Wezel
Subjects: Science
Abstract: Abstract Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition.
Published: 2024
Full Text: View/download PDF

4. Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families

Author: Hogervorst, F.B.L., van Leeuwen, F.E., Adank, M.A., Schmidt, M.K., Stommel-Jenner, D.J., de Groot, R., Vieveen, E., Collée, J.M., Geurts-Giele, W., Heemskerk-Gerritsen, B.A.M., Hooning, M.J., Boere, I.A., van Asperen, C.J., Devilee, P., van der Luijt, R.B., Wevers, M.R., Mensenkamp, A.R., de Hullu, J.A., Ausems, M.G.E.M., Koudijs, M.J., Koole, W., van Engelen, K., Gille, J.J.P., Gómez García, E.B., Blok, M.J., Berger, L.P.V., van der Hout, A.H., de Bock, G.H., Yigit, R., Siesling, S., Verloop, J., Voorham, Q.J.M., Schreurs, Maartje A.C., Schmidt, Marjanka K., Hollestelle, Antoinette, Schaapveld, Michael, van Asperen, Christi J., Ausems, Margreet G.E.M., van de Beek, Irma, Broekema, Marjoleine F., Margriet Collée, J., van der Hout, Annemieke H., van Kaam, Kim J.A.F., Komdeur, Fenne L., Mensenkamp, Arjen R., Adank, Muriel A., and Hooning, Maartje J.
Published: 2024
Full Text: View/download PDF

5. Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines

Author: Luo, Xi, Maciaszek, Jamie L, Thompson, Bryony A, San Leong, Huei, Dixon, Katherine, Sousa, Sónia, Anderson, Michael, Roberts, Maegan E, Lee, Kristy, Spurdle, Amanda B, Mensenkamp, Arjen R, Brannan, Terra, Pardo, Carolina, Zhang, Liying, Pesaran, Tina, Wei, Sainan, Fasaye, Grace-Ann, Kesserwan, Chimene, Shirts, Brian H, Davis, Jeremy L, Oliveira, Carla, Plon, Sharon E, Schrader, Kasmintan A, and Karam, Rachid
Subjects: Genetics, Cancer, Good Health and Well Being, Humans, Genetic Variation, Genetic Testing, Germ-Line Mutation, Stomach Neoplasms, Germ Cells, Antigens, CD, Cadherins, Genetic Predisposition to Disease, Gastrointestinal Diseases, Medical, ClinGen CDH1 Variant Curation Expert Panel, Genetics, Medical, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: BackgroundGermline pathogenic variants in CDH1 are associated with increased risk of diffuse gastric cancer and lobular breast cancer. Risk reduction strategies include consideration of prophylactic surgery, thereby making accurate interpretation of germline CDH1 variants critical for physicians deciding on these procedures. The Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel (VCEP) developed specifications for CDH1 variant curation with a goal to resolve variants of uncertain significance (VUS) and with ClinVar conflicting interpretations and continues to update these specifications.MethodsCDH1 variant classification specifications were modified based on updated genetic testing clinical criteria, new recommendations from ClinGen and expert knowledge from ongoing CDH1 variant curations. The CDH1 VCEP reviewed 273 variants using updated CDH1 specifications and incorporated published and unpublished data provided by diagnostic laboratories.ResultsUpdated CDH1-specific interpretation guidelines include 11 major modifications since the initial specifications from 2018. Using the refined guidelines, 97% (36 of 37) of variants with ClinVar conflicting interpretations were resolved to benign, likely benign, likely pathogenic or pathogenic, and 35% (15 of 43) of VUS were resolved to benign or likely benign. Overall, 88% (239 of 273) of curated variants had non-VUS classifications. To date, variants classified as pathogenic are either nonsense, frameshift, splicing, or affecting the translation initiation codon, and the only missense variants classified as pathogenic or likely pathogenic have been shown to affect splicing.ConclusionsThe development and evolution of CDH1-specific criteria by the expert panel resulted in decreased uncertain and conflicting interpretations of variants in this clinically actionable gene, which can ultimately lead to more effective clinical management recommendations.
Published: 2023

6. A germline PDGFRB splice site variant associated with infantile myofibromatosis and resistance to imatinib

Author: Boulouadnine, Boutaina, Filser, Mathilde, Leducq, Camille, Losole, Taylor, Bies, Joshua, Smetsers, Stephanie, Kouwenberg, Dorus, de Lange, Iris, Mensenkamp, Arjen, Kordes, Uwe Richard, Minard-Colin, Véronique, Orbach, Daniel, Brichard, Bénédicte, de Krijger, Ronald, Masliah-Planchon, Julien, and Demoulin, Jean-Baptiste
Published: 2025
Full Text: View/download PDF

7. The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2

Author: Hinić, Snežana, Cybulski, Cezary, Van der Post, Rachel S., Vos, Janet R., Schuurs-Hoeijmakers, Janneke, Brugnoletti, Fulvia, Koene, Saskia, Vreede, Lilian, van Zelst-Stams, Wendy A.G., Kets, C. Marleen, Haadsma, Maaike, Spruijt, Liesbeth, Wevers, Marijke R., Evans, D. Gareth, Wimmer, Katharina, Schnaiter, Simon, Volk, Alexander E., Möllring, Anna, de Putter, Robin, Soikkonen, Leila, Kahre, Tiina, Tooming, Mikk, de Jong, Mirjam M., Vaz, Fátima, Mensenkamp, Arjen R., Genuardi, Maurizio, Lubinski, Jan, Ligtenberg, Marjolijn, Hoogerbrugge, Nicoline, and de Voer, Richarda M.
Published: 2024
Full Text: View/download PDF

8. Lessons learned from rapid exome sequencing for 575 critically ill patients across the broad spectrum of rare disease

Author: Abderrahim Marouane, Kornelia Neveling, A. Chantal Deden, Simone van den Heuvel, Dimitra Zafeiropoulou, Steven Castelein, Frank van de Veerdonk, David A. Koolen, Annet Simons, Richard Rodenburg, Dineke Westra, Arjen R. Mensenkamp, Nicole de Leeuw, Marjolijn Ligtenberg, Rene Matthijsse, Rolph Pfundt, Erik Jan Kamsteeg, Han G. Brunner, Christian Gilissen, Ilse Feenstra, Willem P. de Boode, Helger G. Yntema, Wendy A. G. van Zelst-Stams, Marcel Nelen, and Lisenka E. L. M. Vissers
Subjects: rapid exome sequencing, diagnostic workflow, turnaround time, clinical outcome, diagnostic yield, Genetics, QH426-470
Abstract: Introduction: Rapid exome sequencing (rES) has become the first-choice genetic test for critically ill patients, mostly neonates, young infants, or fetuses in prenatal care, in time-sensitive situations and when it is expected that the genetic test result may guide clinical decision making. The implementation of rES has revolutionized medicine by enabling timely identification of genetic causes for various rare diseases. The utilization of rES has increasingly been recognized as an essential diagnostic tool for the identification of complex and undiagnosed genetic disorders.Methods: We conducted a retrospective evaluation of our experiences with rES performed on 575 critically ill patients from various age groups (prenatal to adulthood), over a four-year period (2016–2019). These patients presented with a wide spectrum of rare diseases, including but not limited to neurological disorders, severe combined immune deficiency, and cancer.Results: During the study period, there was a significant increase in rES referrals, with a rise from a total of two referrals in Q1-2016 to 10 referrals per week in Q4-2019. The median turnaround time (TAT) decreased from 17 to 11 days in the period 2016–2019, with an overall median TAT of 11 days (IQR 8–15 days). The overall diagnostic yield for this cohort was 30.4%, and did not significantly differ between the different age groups (e.g. adults 22.2% vs children 31.0%; p-value 0.35). However, variability in yield was observed between clinical entities: craniofacial anomalies yielded 58.3%, while for three clinical entities (severe combined immune deficiency, aneurysm, and hypogonadotropic hypogonadism) no diagnoses were obtained.Discussion: Importantly, whereas clinical significance is often only attributed to a conclusive diagnosis, we also observed impact on clinical decision-making for individuals in whom no genetic diagnosis was established. Hence, our experience shows that rES has an important role for patients of all ages and across the broad spectrum of rare diseases to impact clinical outcomes.
Published: 2024
Full Text: View/download PDF

9. Genotype-phenotype associations in a large PTEN Hamartoma Tumor Syndrome (PHTS) patient cohort

Author: Duijkers, Floor, Giltay, Jacques C., van Hest, Liselotte P., Kleefstra, Tjitske, Leter, Edward M., Nielsen, Maartje, Nijmeijer, Sebastiaan W.R., Olderode-Berends, Maran J.W., Hendricks, Linda A.J., Hoogerbrugge, Nicoline, Venselaar, Hanka, Aretz, Stefan, Spier, Isabel, Legius, Eric, Brems, Hilde, de Putter, Robin, Claes, Kathleen B.M., Evans, D. Gareth, Woodward, Emma R., Genuardi, Maurizio, Brugnoletti, Fulvia, van Ierland, Yvette, Dijke, Kim, Tham, Emma, Tesi, Bianca, Schuurs-Hoeijmakers, Janneke H.M., Branchaud, Maud, Salvador, Hector, Jahn, Arne, Schnaiter, Simon, Anastasiadou, Violetta Christophidou, Brunet, Joan, Oliveira, Carla, Roht, Laura, Blatnik, Ana, Irmejs, Arvids, Mensenkamp, Arjen R., and Vos, Janet R.
Published: 2022
Full Text: View/download PDF

10. Noncoding Aberrations in Mismatch Repair Genes Underlie a Substantial Part of the Missing Heritability in Lynch Syndrome

Author: Baert-Desurmont, Stéphanie, Claes, Kathleen B.M., de Leeneer, Kim, Elze, Lisa, van den Heuvel, Simone, van der Post, Rachel S., van Twuijver, Yvonne, van Ham, Tjakko J., Wagner, Anja, de Jong, Mirjam M., Leter, Edward M., Nielsen, Maartje, Te Paske, Iris B.A.W., Mensenkamp, Arjen R., Neveling, Kornelia, Hoogerbrugge, Nicoline, Ligtenberg, Marjolijn J.L., and De Voer, Richarda M.
Published: 2022
Full Text: View/download PDF

11. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author: Barnes, Daniel R., Rookus, Matti A., McGuffog, Lesley, Leslie, Goska, Mooij, Thea M., Dennis, Joe, Mavaddat, Nasim, Adlard, Julian, Ahmed, Munaza, Aittomäki, Kristiina, Andrieu, Nadine, Andrulis, Irene L., Arnold, Norbert, Arun, Banu K., Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berthet, Pascaline, Białkowska, Katarzyna, Blanco, Amie M., Blok, Marinus J., Bonanni, Bernardo, Boonen, Susanne E., Borg, Åke, Bozsik, Aniko, Bradbury, Angela R., Brennan, Paul, Brewer, Carole, Brunet, Joan, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Campbell, Ian, Christensen, Lise Lotte, Chung, Wendy K., Claes, Kathleen B.M., Colas, Chrystelle, Collonge-Rame, Marie-Agnès, Delnatte, Capucine, Faivre, Laurence, Giraud, Sophie, Lasset, Christine, Mari, Véronique, Mebirouk, Noura, Mouret-Fourme, Emmanuelle, Schuster, Hélène, Stoppa-Lyonnet, Dominique, Antoniou, Antonis, Cook, Jackie, Davidson, Rosemarie, Easton, Douglas, Eeles, Ros, Evans, D. Gareth, Frost, Debra, Hanson, Helen, Izatt, Louise, Ong, Kai-ren, Side, Lucy, O’Shaughnessy-Kirwan, Aoife, Tischkowitz, Marc, Walker, Lisa, Daly, Mary B., de la Hoya, Miguel, de Putter, Robin, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dorfling, Cecilia M., Dumont, Martine, Ejlertsen, Bent, Engel, Christoph, Foretova, Lenka, Fostira, Florentia, Friedlander, Michael, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., González-Neira, Anna, Greene, Mark H., Gschwantler-Kaulich, Daphne, Hahnen, Eric, Hamann, Ute, Hentschel, Julia, Hogervorst, Frans B.L., Hooning, Maartje J., Horvath, Judit, Hu, Chunling, Hulick, Peter J., Imyanitov, Evgeny N., Chenevix-Trench, Georgia, Phillips, Kelly-Anne, Spurdle, Amanda, Blok, Marinus, Hogervorst, Frans, Hooning, Maartje, Koudijs, Marco, Mensenkamp, Arjen, Meijers-Heijboer, Hanne, Rookus, Matti, Engelen, Klaartje van, Noguès, Catherine, Isaacs, Claudine, Izquierdo, Angel, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, John, Esther M., Joseph, Vijai, Karlan, Beth Y., Kast, Karin, Kruse, Torben A., Kwong, Ava, Laitman, Yael, Lazaro, Conxi, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Loud, Jennifer T., Lubiński, Jan, Mai, Phuong L., Manoukian, Siranoush, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Miller, Austin, Montagna, Marco, Mukherjee, Semanti, Mulligan, Anna Marie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn Cilius, Nikitina-Zake, Liene, Olah, Edith, Olopade, Olufunmilayo I., Osorio, Ana, Ott, Claus-Eric, Papi, Laura, Park, Sue K., Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Peixoto, Ana, Peterlongo, Paolo, Pfeiler, Georg, Prajzendanc, Karolina, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Ramus, Susan J., Rantala, Johanna, Rennert, Gad, Risch, Harvey A., Robson, Mark, Rønlund, Karina, Salani, Ritu, Senter, Leigha, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Singer, Christian F., Slavin, Thomas P., Soucy, Penny, Southey, Melissa C., Spurdle, Amanda B., Steinemann, Doris, Steinsnyder, Zoe, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Thull, Darcy L., Tognazzo, Silvia, Toland, Amanda E., Trainer, Alison H., Tung, Nadine, van Engelen, Klaartje, van Rensburg, Elizabeth J., Vega, Ana, Vierstraete, Jeroen, Wagner, Gabriel, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Yadav, Siddhartha, Yang, Xin, Yannoukakos, Drakoulis, Zimbalatti, Dario, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., and Antoniou, Antonis C.
Published: 2020
Full Text: View/download PDF

12. Catch them if you are aware: PTEN postzygotic mosaicism in clinically suspicious patients with PTEN Hamartoma Tumour Syndrome and literature review

Author: Hendricks, Linda A.J., Schuurs-Hoeijmakers, Janneke, Spier, Isabel, Haadsma, Maaike L., Eijkelenboom, Astrid, Cremer, Kirsten, Mensenkamp, Arjen R., Aretz, Stefan, Vos, Janet R., and Hoogerbrugge, Nicoline
Published: 2022
Full Text: View/download PDF

13. Genomic instability in non–breast or ovarian malignancies of individuals with germline pathogenic variants in BRCA1/2.

Author: Elze, Lisa, Post, Rachel S van der, Vos, Janet R, Mensenkamp, Arjen R, Naga, Samhita Pamidimarri, Hampstead, Juliet E, Vermeulen, Emma, Oorsprong, Michiel, Hofste, Tom, Simons, Michiel, Nagtegaal, Iris D, Hoogerbrugge, Nicoline, Voer, Richarda M de, and Ligtenberg, Marjolijn J L
Subjects: HOMOLOGOUS recombination, WHOLE genome sequencing, BRCA genes, GENOMICS, NUCLEOTIDE sequencing
Abstract: Background Individuals with germline pathogenic variants in BRCA1 or BRCA2 are at a high risk of breast and ovarian carcinomas with BRCA1/2 deficiency and homologous recombination deficiency that can be detected by analysis of genome-wide genomic instability features such as large-scale state transitions, telomeric allelic imbalances, and genomic loss of heterozygosity. Malignancies with homologous recombination deficiency are more sensitive to platinum-based therapies and poly(ADP-ribose) polymerase inhibitors. We investigated the fraction of non–breast or ovarian malignancies that have BRCA1/2 deficiency and genomic instability features. Methods The full tumor history of a large, historical, clinic-based, consecutive cohort of 2965 individuals with germline pathogenic variants in BRCA1 /2 was retrieved from the Dutch nationwide pathology databank (Palga). In total, 169 non–breast or ovarian malignancies were collected and analyzed using targeted next-generation sequencing and shallow whole-genome sequencing to determine somatic second-hit alterations and genomic instabilities indicative of homologous recombination deficiency, respectively. Results BRCA1/2 deficiency was detected in 27% (21/79) and 23% (21/90) of 20 different types of non–breast or ovarian malignancies in individuals with germline pathogenic variants in BRCA1 and BRCA2, respectively. These malignancies had a higher genomic instability score than BRCA1 - or BRCA2 -proficient malignancies (P < .001 and P < .001, respectively). Conclusions BRCA1/2 deficiency and genomic instability features were found in 27% and 23% of a broad spectrum of non–breast or ovarian malignancies in individuals with germline pathogenic variants in BRCA1 and BRCA2, respectively. Evaluation of the effectiveness of poly(ADP-ribose) polymerase inhibitors in these individuals should be focused on tumors with a confirmed absence of a wild-type allele. [ABSTRACT FROM AUTHOR]
Published: 2024
Full Text: View/download PDF

14. Histopathological phenotyping of cancers in PTEN Hamartoma Tumor Syndrome for improved recognition: A single‐center study.

Author: Schei‐Andersen, Ane J., Hendricks, Linda A. J., van der Post, Rachel S., Mensenkamp, Arjen R., Schieving, Jolanda, Adank, Muriel A., Duijkers, Floor, de Jong, Mirjam, Jongemans, Marjolijn C. J., van Hest, Liselotte P., van Ierland, Yvette, Kleefstra, Tjitske, Leter, Edward M., Nielsen, Maartje, Schuurs‐Hoeijmakers, Janneke H. M., Hoogerbrugge, Nicoline, and Vos, Janet R.
Subjects: HEREDITARY cancer syndromes, DISEASE risk factors, AGE of onset, BENIGN tumors, HUMAN genetics
Abstract: PTEN hamartoma tumor syndrome (PHTS) has a broad clinical spectrum including various benign and malignant tumors at varying age of diagnosis. Many patients remain unrecognized, unaware of their increased cancer risk. We aimed to describe the cancer spectrum, age of onset and histopathological cancer characteristics to assess whether specific cancer characteristics could improve PHTS recognition. Genetic testing results and pathology reports were collected for patients tested for germline PTEN variants between 1997 and 2020 from the diagnostic laboratory and the Dutch nationwide pathology databank (Palga). The cancer spectrum and age of onset were assessed in patients with (PTENpos) and without (PTENneg) a germline PTEN variant. Histopathological cancer characteristics were assessed in a nested cohort. 341 PTENpos patients (56% females) and 2882 PTENneg patients (66% females) were included. PTENpos patients presented mostly with female breast (BC, 30%), endometrial (EC, 6%), thyroid (TC, 4%) or colorectal cancer (4%). PTENpos were significantly younger at cancer onset (43 vs. 47 years) and had more often (46% vs. 18%) a second BC than PTENneg. PTEN detection rates were highest for BC <40 years (9%), TC <20 years (15%) and EC <50 years (28%), and dropped to 6%, 4%, and 15% by age 60. Histopathological characteristics were similar between groups. No histopathological cancer characteristics were distinctive for PHTS. However, PTENpos were significantly younger at cancer onset. Therefore early‐onset BC, EC, or TC warrants consideration of PHTS diagnostics either through a pre‐screen for other PHTS features or direct germline testing. [ABSTRACT FROM AUTHOR]
Published: 2024
Full Text: View/download PDF

15. Genetic Cancer Susceptibility in Adolescents and Adults 25 Years or Younger With Colorectal Cancer

Author: Mensenkamp, Arjen R., van Kessel, Ad Geurts, Spruijt, Liesbeth, Kets, C. Marleen, van Zelst-Stam, Wendy A.G., Schouten, Meyke I., Wevers, Marijke R., Olderode-Berends, Maran J.W., Oosterwijk, Jan C., Hitzert, Marrit M., Letteboer, Tom G.W., Stanković, Snežana, Kamping, Eveline J., Yuniati, Laurensia, van Leeuwen, Frank N., Weitz, Jürgen, van der Post, Rachel S., Teixeira, Manuel R., Liu, Huanliang, Wang, Jianping, Jongmans, Marjolijn C.J., Zhang, Junxiao, Kuiper, Roland P., Hoogerbrugge, Nicoline, Ligtenberg, Marjolijn J.L., and De Voer, Richarda M.
Published: 2022
Full Text: View/download PDF

16. Securing Home Wi-Fi with WPA3 Personal.

Author: Erik Lamers, Raoul Dijksman Mensenkamp, Arjan van der Vegt, Mayur Sarode, and Cees de Laat
Published: 2021
Full Text: View/download PDF

17. P076: The ClinGen ENIGMA BRCA1/2 expert panel: A dynamic framework for evidence-based recommendations to improve classification criteria for variants in BRCA1/2

Author: Michael Parsons, Michael Anderson, Windy Berkofsky-Fessler, Sandrine Caputo, Raymond Chan, Melissa Cline, Fergus Couch, Miguel de la Hoya, Bing-Jian Feng, David Goldgar, Encarna Gomez-Garcia, Susan Hiraki, Megan Holdren, Claude Houdayer, Paul James, Rachid Karam, Huei San Leong, Alexandra Martins, Arjen Mensenkamp, Alvaro Monteiro, Vaishnavi Nathan, Robert O'Connor, Tina Pesaran, Paolo Radice, Marcy Richardson, Gunnar Schmidt, Inge Sokilde Pedersen, Melissa Southey, Sean Tavtigian, Bryony Thompson, Amanda Toland, Emma Tudini, Clare Turnbull, Maaike Vreeswijk, Logan Walker, Lauren Zec, and Amanda Spurdle
Subjects: Genetics, QH426-470, Medicine
Published: 2023
Full Text: View/download PDF

18. The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Author: Lakeman, Inge M.M., van den Broek, Alexandra J., Vos, Juliën A.M., Barnes, Daniel R., Adlard, Julian, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Balmaña, Judith, Barrowdale, Daniel, Benitez, Javier, Borg, Ake, Caldés, Trinidad, Caligo, Maria A., Chung, Wendy K., Claes, Kathleen B.M., Barouk-Simonet, Emmanuelle, Belotti, Muriel, Berthet, Pascaline, Bignon, Yves-Jean, Bonadona, Valérie, Bressac-de Paillerets, Brigitte, Buecher, Bruno, Caputo, Sandrine, Caron, Olivier, Castera, Laurent, Caux-Moncoutier, Virginie, Colas, Chrystelle, Collonge-Rame, Marie-Agnès, Coupier, Isabelle, de Pauw, Antoine, Delnatte, Capucine, Elan, Camille, Faivre, Laurence, Ferrer, Sandra Fert, Gauthier-Villars, Marion, Gesta, Paul, Giraud, Sophie, Golmard, Lisa, Houdayer, Claude, Lasset, Christine, Laurent, Maïté, Leroux, Dominique, Longy, Michel, Mari, Véronique, Mazoyer, Sylvie, Mebirouk, Noura, Mortemousque, Isabelle, Prieur, Fabienne, Pujol, Pascal, Saule, Claire, Schuster, Helene, Sevenet, Nicolas, Sobol, Hagay, Sokolowska, Johanna, Venat-Bouvet, Laurence, Ahmed, Munaza, Barwell, Julian, Brady, Angela, Brennan, Paul, Brewer, Carole, Cook, Jackie, Davidson, Rosemarie, Donaldson, Alan, Dunning, Alison M., Eason, Jacqueline, Eccles, Diana M., Gregory, Helen, Hanson, Helen, Harrington, Patricia A., Henderson, Alex, Hodgson, Shirley, Kennedy, M. John, Lalloo, Fiona, Miller, Clare, Morrison, Patrick J., Ong, Kai-ren, O’Shaughnessy-Kirwan, Aoife, Perkins, Jo, Porteous, Mary E., Rogers, Mark T., Side, Lucy E., Snape, Katie, Walker, Lisa, Collée, J. Margriet, Couch, Fergus J., Daly, Mary B., Dennis, Joe, Dhawan, Mallika, Domchek, Susan M., Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadaló, Lidia, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Gayther, Simon A., Gerdes, Anne-Marie, Godwin, Andrew K., Goldgar, David E., Hahnen, Eric, Hake, Christopher R., Hamann, Ute, Hogervorst, Frans B.L., Hooning, Maartje J., Hopper, John L., Hulick, Peter J., Imyanitov, Evgeny N., Glendon, Gord, Mulligan, Anna Marie, van Asperen, Christi J., Aalfs, Cora M., Adank, Muriel A., Ausems, Margreet G.E.M., Blok, Marinus J., Gómez Garcia, Encarna B., Heemskerk-Gerritsen, Bernadette A.M., Hollestelle, Antoinette, Jager, Agnes, Koppert, Linetta B., Koudijs, Marco, Kriege, Mieke, Meijers-Heijboer, Hanne E.J., Mensenkamp, Arjen R., Mooij, Thea M., Oosterwijk, Jan C., van den Ouweland, Ans M.W., van der Baan, Frederieke H., van der Hout, Annemieke H., van der Kolk, Lizet E., van der Luijt, Rob B., van Deurzen, Carolien H.M., van Doorn, Helena C., van Engelen, Klaartje, van Hest, Liselotte P., van Os, Theo A.M., Verhoef, Senno, Vogel, Maartje J., Wijnen, Juul T., Beesley, Jonathan, Fox, Stephen, Holland, Helene, Phillips, Kelly-Anne, Spurdle, Amanda B., Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Jiao, Yue, John, Esther M., Joseph, Vijai, Karlan, Beth Y., Kets, Carolien M., Konstantopoulou, Irene, Kwong, Ava, Legrand, Clémentine, Leslie, Goska, Lesueur, Fabienne, Loud, Jennifer T., Lubiński, Jan, Manoukian, Siranoush, McGuffog, Lesley, Miller, Austin, Gomes, Denise Molina, Montagna, Marco, Mouret-Fourme, Emmanuelle, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Olah, Edith, Olopade, Olufunmilayo I., Park, Sue K., Parsons, Michael T., Peterlongo, Paolo, Piedmonte, Marion, Radice, Paolo, Rantala, Johanna, Rennert, Gad, Risch, Harvey A., Schmutzler, Rita K., Sharma, Priyanka, Simard, Jacques, Singer, Christian F., Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Teulé, Alex, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, van Rensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Devilee, Peter, Bernstein, Jonine L., Offit, Kenneth, Easton, Douglas F., Rookus, Matti A., Chenevix-Trench, Georgia, Antoniou, Antonis C., Robson, Mark, and Schmidt, Marjanka K.
Published: 2021
Full Text: View/download PDF

19. Clinical, Pathology, Genetic, and Molecular Features of Colorectal Tumors in Adolescents and Adults 25 Years or Younger

Author: de Voer, Richarda M., Diets, Illja J., van der Post, Rachel S., Weren, Robbert D.A., Kamping, Eveline J., de Bitter, Tessa J.J., Elze, Lisa, Verhoeven, Rob H.A., Vink-Börger, Elisa, Eijkelenboom, Astrid, Mensenkamp, Arjen, Nagtegaal, Iris D., Jongmans, Marjolijn C.J., and Ligtenberg, Marjolijn J.L.
Published: 2021
Full Text: View/download PDF

20. Somatic Nonepigenetic Mismatch Repair Gene Aberrations Underly Most Mismatch Repair–Deficient Lynch-Like Tumors

Author: Dommering, Charlotte J., Hoogerbrugge, Nicoline, de Jong, Mirjam M., Bleeker, Fonnet E., Leter, Edward M., Letteboer, Tom G.W., Nielsen, Maartje, van der Post, Rachel S., Wapstra, Brigit, Elze, Lisa, Mensenkamp, Arjen R., Nagtegaal, Iris D., van Zelst-Stams, Wendy A.G., de Voer, Richarda M., and Ligtenberg, Marjolijn J.L.
Published: 2021
Full Text: View/download PDF

21. Wi-Fi 6 performance measurements of 1024-QAM and DL OFDMA.

Author: Daan Weller, Raoul Dijksman Mensenkamp, Arjan van der Vegt, Jan-Willem van Bloem, and Cees de Laat
Published: 2020
Full Text: View/download PDF

22. The genomic landscape of breast and non-breast cancers from individuals with germline CHEK2 deficiency.

Author: Hinić, Snežana, Post, Rachel S van der, Vreede, Lilian, Schuurs-Hoeijmakers, Janneke, Koene, Saskia, Jansen, Erik A M, Bervoets-Metge, Franziska, Mensenkamp, Arjen R, Hoogerbrugge, Nicoline, Ligtenberg, Marjolijn J L, and Voer, Richarda M de
Subjects: CHECKPOINT kinase 2, BREAST cancer, HOMOLOGOUS recombination, GERM cells, BRCA genes
Abstract: CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency—for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2 -deficient cancers. [ABSTRACT FROM AUTHOR]
Published: 2024
Full Text: View/download PDF

23. Lifestyle Factors and Breast Cancer in Females with PTEN Hamartoma Tumor Syndrome (PHTS)

Author: Hendricks, Linda A. J., primary, Verbeek, Katja C. J., additional, Schuurs-Hoeijmakers, Janneke H. M., additional, Mensenkamp, Arjen R., additional, Brems, Hilde, additional, de Putter, Robin, additional, Anastasiadou, Violetta C., additional, Villy, Marie-Charlotte, additional, Jahn, Arne, additional, Steinke-Lange, Verena, additional, Baldassarri, Margherita, additional, Irmejs, Arvids, additional, de Jong, Mirjam M., additional, Links, Thera P., additional, Leter, Edward M., additional, Bosch, Daniëlle G. M., additional, Høberg-Vetti, Hildegunn, additional, Tveit Haavind, Marianne, additional, Jørgensen, Kjersti, additional, Mæhle, Lovise, additional, Blatnik, Ana, additional, Brunet, Joan, additional, Darder, Esther, additional, Tham, Emma, additional, Hoogerbrugge, Nicoline, additional, and Vos, Janet R., additional
Published: 2024
Full Text: View/download PDF

24. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

Author: Vigorito, Elena, Kuchenbaecker, Karoline B, Beesley, Jonathan, Adlard, Julian, Agnarsson, Bjarni A, Andrulis, Irene L, Arun, Banu K, Barjhoux, Laure, Belotti, Muriel, Benitez, Javier, Berger, Andreas, Bojesen, Anders, Bonanni, Bernardo, Brewer, Carole, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Chan, Salina B, Claes, Kathleen BM, Cohn, David E, Cook, Jackie, Daly, Mary B, Damiola, Francesca, Davidson, Rosemarie, Pauw, Antoine de, Delnatte, Capucine, Diez, Orland, Domchek, Susan M, Dumont, Martine, Durda, Katarzyna, Dworniczak, Bernd, Easton, Douglas F, Eccles, Diana, Edwinsdotter Ardnor, Christina, Eeles, Ros, Ejlertsen, Bent, Ellis, Steve, Evans, D Gareth, Feliubadalo, Lidia, Fostira, Florentia, Foulkes, William D, Friedman, Eitan, Frost, Debra, Gaddam, Pragna, Ganz, Patricia A, Garber, Judy, Garcia-Barberan, Vanesa, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Giraud, Sophie, Godwin, Andrew K, Goldgar, David E, Hake, Christopher R, Hansen, Thomas VO, Healey, Sue, Hodgson, Shirley, Hogervorst, Frans BL, Houdayer, Claude, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jacobs, Lauren, Jakubowska, Anna, Janavicius, Ramunas, Jaworska-Bieniek, Katarzyna, Jensen, Uffe Birk, John, Esther M, Vijai, Joseph, Karlan, Beth Y, Kast, Karin, KConFab Investigators, Khan, Sofia, Kwong, Ava, Laitman, Yael, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lubinski, Jan, Mai, Phuong L, Manoukian, Siranoush, Mazoyer, Sylvie, Meindl, Alfons, Mensenkamp, Arjen R, Montagna, Marco, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I, Ong, Kai-Ren, Osorio, Ana, Park, Sue Kyung, Paulsson-Karlsson, Ylva, Pedersen, Inge Sokilde, Peissel, Bernard, and Peterlongo, Paolo
Subjects: KConFab Investigators, Chromosomes, Human, Pair 9, Humans, Ovarian Neoplasms, Genetic Predisposition to Disease, Chromosome Mapping, Polymorphism, Single Nucleotide, Genes, BRCA1, Genes, BRCA2, Female, Genetic Carrier Screening, General Science & Technology
Abstract: Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
Published: 2016

25. Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families

Author: Genetica Klinische Genetica, Cancer, Afdeling Dietetiek, Hubrecht Institute with UMC, Genetica Sectie Genoomdiagnostiek, MS CGO, Epi Kanker Team A, Schreurs, Maartje A.C., Schmidt, Marjanka K., Hollestelle, Antoinette, Schaapveld, Michael, van Asperen, Christi J., Ausems, Margreet G.E.M., van de Beek, Irma, Broekema, Marjoleine F., Margriet Collée, J., van der Hout, Annemieke H., van Kaam, Kim J.A.F., Komdeur, Fenne L., Mensenkamp, A. R., Adank, M. A., Hooning, M. J., The Hereditary Breast and Ovarian Cancer Research Group Netherlands, Genetica Klinische Genetica, Cancer, Afdeling Dietetiek, Hubrecht Institute with UMC, Genetica Sectie Genoomdiagnostiek, MS CGO, Epi Kanker Team A, Schreurs, Maartje A.C., Schmidt, Marjanka K., Hollestelle, Antoinette, Schaapveld, Michael, van Asperen, Christi J., Ausems, Margreet G.E.M., van de Beek, Irma, Broekema, Marjoleine F., Margriet Collée, J., van der Hout, Annemieke H., van Kaam, Kim J.A.F., Komdeur, Fenne L., Mensenkamp, A. R., Adank, M. A., Hooning, M. J., and The Hereditary Breast and Ovarian Cancer Research Group Netherlands
Published: 2024

26. Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families

Author: Schreurs, Maartje A.C., Schmidt, Marjanka K., Hollestelle, Antoinette, Schaapveld, Michael, van Asperen, Christi J., Ausems, M. G.E.M., van de Beek, Irma, Broekema, Marjoleine F., Margriet Collée, J., van der Hout, Annemieke H., van Kaam, Kim J.A.F., Komdeur, Fenne L., Mensenkamp, A. R., Adank, Muriel A., Hooning, Maartje J., Schreurs, Maartje A.C., Schmidt, Marjanka K., Hollestelle, Antoinette, Schaapveld, Michael, van Asperen, Christi J., Ausems, M. G.E.M., van de Beek, Irma, Broekema, Marjoleine F., Margriet Collée, J., van der Hout, Annemieke H., van Kaam, Kim J.A.F., Komdeur, Fenne L., Mensenkamp, A. R., Adank, Muriel A., and Hooning, Maartje J.
Abstract: Purpose: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families. Methods:Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women. Results: We found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward. Conclusion: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance.
Published: 2024

27. Lifestyle Factors and Breast Cancer in Females with PTEN Hamartoma Tumor Syndrome (PHTS)

Author: Hendricks, Linda A.J., Verbeek, Katja C.J., Schuurs-Hoeijmakers, Janneke H.M., Mensenkamp, Arjen R., Brems, Hilde, de Putter, Robin, Anastasiadou, Violetta C., Villy, Marie Charlotte, Jahn, Arne, Steinke-Lange, Verena, Baldassarri, Margherita, Irmejs, Arvids, de Jong, Mirjam M., Links, Thera P., Leter, Edward M., Bosch, Daniëlle G.M., Høberg-Vetti, Hildegunn, Tveit Haavind, Marianne, Jørgensen, Kjersti, Mæhle, Lovise, Blatnik, Ana, Brunet, Joan, Darder, Esther, Tham, Emma, Hoogerbrugge, Nicoline, Vos, Janet R., Hendricks, Linda A.J., Verbeek, Katja C.J., Schuurs-Hoeijmakers, Janneke H.M., Mensenkamp, Arjen R., Brems, Hilde, de Putter, Robin, Anastasiadou, Violetta C., Villy, Marie Charlotte, Jahn, Arne, Steinke-Lange, Verena, Baldassarri, Margherita, Irmejs, Arvids, de Jong, Mirjam M., Links, Thera P., Leter, Edward M., Bosch, Daniëlle G.M., Høberg-Vetti, Hildegunn, Tveit Haavind, Marianne, Jørgensen, Kjersti, Mæhle, Lovise, Blatnik, Ana, Brunet, Joan, Darder, Esther, Tham, Emma, Hoogerbrugge, Nicoline, and Vos, Janet R.
Abstract: Females with PTEN Hamartoma Tumor Syndrome (PHTS) have breast cancer risks up to 76%. This study assessed associations between breast cancer and lifestyle in European female adult PHTS patients. Data were collected via patient questionnaires (July 2020–March 2023) and genetic diagnoses from medical files. Associations between lifestyle and breast cancer were calculated using logistic regression corrected for age. Index patients with breast cancer before PHTS diagnosis (breast cancer index) were excluded for ascertainment bias correction. In total, 125 patients were included who completed the questionnaire at a mean age of 44 years (SD = 13). This included 21 breast cancer indexes (17%) and 39 females who developed breast cancer at 43 years (SD = 9). Breast cancer patients performed about 1.1 times less often 0–1 times/week physical activity than ≥2 times (ORtotal-adj = 0.9 (95%CI 0.3–2.6); consumed daily about 1.2–1.8 times more often ≥1 than 0–1 glasses of alcohol (ORtotal-adj = 1.2 (95%CI 0.4–4.0); ORnon-breastcancer-index-adj = 1.8 (95%CI 0.4–6.9); were about 1.04–1.3 times more often smokers than non-smokers (ORtotal-adj = 1.04 (95%CI 0.4–2.8); ORnon-breastcancer-index-adj = 1.3 (95%CI 0.4–4.2)); and overweight or obesity (72%) was about 1.02–1.3 times less common (ORtotal-adj = 0.98 (95%CI 0.4–2.6); ORnon-breastcancer-index-adj = 0.8 (95%CI 0.3–2.7)). Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients’ breast cancer risk is important.
Published: 2024

28. Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel

Author: Parsons, Michael T., primary, de la Hoya, Miguel, additional, Richardson, Marcy E., additional, Tudini, Emma, additional, Anderson, Michael, additional, Berkofsky-Fessler, Windy, additional, Caputo, Sandrine, additional, Chan, Raymond C., additional, Cline, Melissa C., additional, Feng, Bing-Jian, additional, Fortuno, Cristina, additional, Gomez-Garcia, Encarna, additional, Hadler, Johanna, additional, Hiraki, Susan, additional, Holdren, Megan, additional, Houdayer, Claude, additional, Hruska, Kathleen, additional, James, Paul, additional, Karam, Rachid, additional, Leong, Huei San, additional, Martins, Alexandra, additional, Mensenkamp, Arjen R., additional, Monteiro, Alvaro N., additional, Nathan, Vaishnavi, additional, O'Connor, Robert, additional, Pesaran, Tina, additional, Radice, Paolo, additional, Schmidt, Gunnar, additional, Sokilde-Pedersen, Inge, additional, Southey, Melissa, additional, Tavtigian, Sean V., additional, Thompson, Bryony A., additional, Toland, Amanda E., additional, Turnbull, Clare, additional, Vogel, Maartje J., additional, Weyandt, Jamie, additional, Wiggins, George A.R., additional, Zec, Lauren, additional, Couch, Fergus J., additional, Walker, Logan, additional, Vreeswijk, Maaike P.G., additional, Goldgar, David E., additional, and Spurdle, Amanda B., additional
Published: 2024
Full Text: View/download PDF

29. Lessons learned from rapid exome sequencing for 575 critically ill patients across the broad spectrum of rare disease

Author: Marouane, Abderrahim, primary, Neveling, Kornelia, additional, Deden, A. Chantal, additional, van den Heuvel, Simone, additional, Zafeiropoulou, Dimitra, additional, Castelein, Steven, additional, van de Veerdonk, Frank, additional, Koolen, David A., additional, Simons, Annet, additional, Rodenburg, Richard, additional, Westra, Dineke, additional, Mensenkamp, Arjen R., additional, de Leeuw, Nicole, additional, Ligtenberg, Marjolijn, additional, Matthijsse, Rene, additional, Pfundt, Rolph, additional, Kamsteeg, Erik Jan, additional, Brunner, Han G., additional, Gilissen, Christian, additional, Feenstra, Ilse, additional, de Boode, Willem P., additional, Yntema, Helger G., additional, van Zelst-Stams, Wendy A. G., additional, Nelen, Marcel, additional, and Vissers, Lisenka E. L. M., additional
Published: 2024
Full Text: View/download PDF

30. Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Author: Peer Arts, Annet Simons, Mofareh S. AlZahrani, Elanur Yilmaz, Eman AlIdrissi, Koen J. van Aerde, Njood Alenezi, Hamza A. AlGhamdi, Hadeel A. AlJubab, Abdulrahman A. Al-Hussaini, Fahad AlManjomi, Alaa B. Alsaad, Badr Alsaleem, Abdulrahman A. Andijani, Ali Asery, Walid Ballourah, Chantal P. Bleeker-Rovers, Marcel van Deuren, Michiel van der Flier, Erica H. Gerkes, Christian Gilissen, Murad K. Habazi, Jayne Y. Hehir-Kwa, Stefanie S. Henriet, Esther P. Hoppenreijs, Sarah Hortillosa, Chantal H. Kerkhofs, Riikka Keski-Filppula, Stefan H. Lelieveld, Khurram Lone, Marius A. MacKenzie, Arjen R. Mensenkamp, Jukka Moilanen, Marcel Nelen, Jaap ten Oever, Judith Potjewijd, Pieter van Paassen, Janneke H. M. Schuurs-Hoeijmakers, Anna Simon, Tomasz Stokowy, Maartje van de Vorst, Maaike Vreeburg, Anja Wagner, Gijs T. J. van Well, Dimitra Zafeiropoulou, Evelien Zonneveld-Huijssoon, Joris A. Veltman, Wendy A. G. van Zelst-Stams, Eissa A. Faqeih, Frank L. van de Veerdonk, Mihai G. Netea, and Alexander Hoischen
Subjects: Routine diagnostics, Genetic diagnosis, Exome sequencing, Primary immunodeficiencies, Medicine, Genetics, QH426-470
Abstract: Abstract Background Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test. Methods In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs. This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by autoimmune manifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations, aberrant antibody levels, or combinations of these factors. Results For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%). Conclusion Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data.
Published: 2019
Full Text: View/download PDF

31. Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset

Author: Sahlberg, Kristine K., Børresen-Dale, Anne-Lise, Gram, Inger Torhild, Olsen, Karina Standahl, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, OSBREAC, Grenaker Alnæs, Grethe I., Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, Dawson, Sarah-Jane, deFazio, Anna, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Gaff, Clara, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Hart, Stewart, Harraka, Philip, Hayward, Nick, Hopper, John, Hoskins, Cass, Hunt, Clare, Jenkins, Mark, Kidd, Alexa, Kirk, Judy, Koehler, Jessica, Kollias, James, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason, Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Lobb, Liz, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Meiser, Bettina, Nightingale, Sophie, O'Connell, Shona, O'Sullivan, Sarah, Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Pearn, Amy, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Saleh, Mona, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Savas, Peter, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta, Simpson, Peter, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, Alison, Tucker, Kathy, Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, Ingrid, Young, Mary Ann, Zaheed, Milita, Davidson, Aimee L., Michailidou, Kyriaki, Parsons, Michael T., Fortuno, Cristina, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Naven, Marc, Abubakar, Mustapha, Ahearn, Thomas U., Alonso, M. Rosario, Andrulis, Irene L., Antoniou, Antonis C., Auvinen, Päivi, Behrens, Sabine, Bermisheva, Marina A., Bogdanova, Natalia V., Bojesen, Stig E., Brüning, Thomas, Byers, Helen J., Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Cessna, Melissa H., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J. Margriet, Czene, Kamila, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, Glendon, Gord, González-Neira, Anna, Grassmann, Felix, Gronwald, Jacek, Guénel, Pascal, Hadjisavvas, Andreas, Haeberle, Lothar, Hall, Per, Hamann, Ute, Hartman, Mikael, Ho, Peh Joo, Hooning, Maartje J., Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Khusnutdinova, Elza K., Kristensen, Vessela N., Li, Jingmei, Lim, Joanna, Lindblom, Annika, Liu, Jenny, Lophatananon, Artitaya, Mannermaa, Arto, Mavroudis, Dimitrios A., Mensenkamp, Arjen R., Milne, Roger L., Muir, Kenneth R., Newman, William G., Obi, Nadia, Panayiotidis, Mihalis I., Park, Sue K., Park-Simon, Tjoung-Won, Peterlongo, Paolo, Radice, Paolo, Rashid, Muhammad U., Rhenius, Valerie, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Marjanka K., Seibold, Petra, Shah, Mitul, Southey, Melissa C., Teo, Soo Hwang, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van de Beek, Irma, van der Hout, Annemieke H., Wendt, Camilla C., Dunning, Alison M., Pharoah, Paul D.P., Devilee, Peter, Easton, Douglas F., James, Paul A., and Spurdle, Amanda B.
Published: 2024
Full Text: View/download PDF

32. Renal cell carcinoma in young FH mutation carriers: case series and review of the literature

Author: Hol, J. A., Jongmans, M. C. J., Littooij, A. S., de Krijger, R. R., Kuiper, R. P., van Harssel, J. J. T., Mensenkamp, A., Simons, M., Tytgat, G. A. M., van den Heuvel-Eibrink, M. M., and van Grotel, M.
Published: 2020
Full Text: View/download PDF

33. TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort

Author: Bakhuizen, J. J., Hogervorst, F. B., Velthuizen, M. E., Ruijs, M. W., van Engelen, K., van Os, T. A., Gille, J. J., Collée, M., van den Ouweland, A. M., van Asperen, C. J., Kets, C. M., Mensenkamp, A. R., Leter, E. M., Blok, M. J., de Jong, M. M., and Ausems, M. G.
Published: 2019
Full Text: View/download PDF

34. TINF2 is a haploinsufficient tumor suppressor that limits telomere length

Author: Isabelle Schmutz, Arjen R Mensenkamp, Kaori K Takai, Maaike Haadsma, Liesbeth Spruijt, Richarda M de Voer, Seunga Sara Choo, Franziska K Lorbeer, Emma J van Grinsven, Dirk Hockemeyer, Marjolijn CJ Jongmans, and Titia de Lange
Subjects: cancer predisposition, TIN2, telomere length, Medicine, Science, Biology (General), QH301-705.5
Abstract: Telomere shortening is a presumed tumor suppressor pathway that imposes a proliferative barrier (the Hayflick limit) during tumorigenesis. This model predicts that excessively long somatic telomeres predispose to cancer. Here, we describe cancer-prone families with two unique TINF2 mutations that truncate TIN2, a shelterin subunit that controls telomere length. Patient lymphocyte telomeres were unusually long. We show that the truncated TIN2 proteins do not localize to telomeres, suggesting that the mutations create loss-of-function alleles. Heterozygous knock-in of the mutations or deletion of one copy of TINF2 resulted in excessive telomere elongation in clonal lines, indicating that TINF2 is haploinsufficient for telomere length control. In contrast, telomere protection and genome stability were maintained in all heterozygous clones. The data establish that the TINF2 truncations predispose to a tumor syndrome. We conclude that TINF2 acts as a haploinsufficient tumor suppressor that limits telomere length to ensure a timely Hayflick limit.
Published: 2020
Full Text: View/download PDF

35. Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

Author: Pfundt, Rolph, del Rosario, Marisol, Vissers, Lisenka E.L.M., Kwint, Michael P., Janssen, Irene M., de Leeuw, Nicole, Yntema, Helger G., Nelen, Marcel R., Lugtenberg, Dorien, Kamsteeg, Erik-Jan, Wieskamp, Nienke, Stegmann, Alexander P.A., Stevens, Servi J.C., Rodenburg, Richard J.T., Simons, Annet, Mensenkamp, Arjen R., Rinne, Tuula, Gilissen, Christian, Scheffer, Hans, Veltman, Joris A., Prof. Dr, and Hehir-Kwa, Jayne Y.
Published: 2017
Full Text: View/download PDF

36. Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines

Author: Xi Luo, Jamie L Maciaszek, Bryony A Thompson, Huei San Leong, Katherine Dixon, Sónia Sousa, Michael Anderson, Maegan E Roberts, Kristy Lee, Amanda B Spurdle, Arjen R Mensenkamp, Terra Brannan, Carolina Pardo, Liying Zhang, Tina Pesaran, Sainan Wei, Grace-Ann Fasaye, Chimene Kesserwan, Brian H Shirts, Jeremy L Davis, Carla Oliveira, Sharon E Plon, Kasmintan A Schrader, and Rachid Karam
Subjects: All institutes and research themes of the Radboud University Medical Center, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Genetics, Genetics (clinical)
Abstract: BackgroundGermline pathogenic variants inCDH1are associated with increased risk of diffuse gastric cancer and lobular breast cancer. Risk reduction strategies include consideration of prophylactic surgery, thereby making accurate interpretation of germlineCDH1variants critical for physicians deciding on these procedures. The Clinical Genome Resource (ClinGen)CDH1Variant Curation Expert Panel (VCEP) developed specifications forCDH1variant curation with a goal to resolve variants of uncertain significance (VUS) and with ClinVar conflicting interpretations and continues to update these specifications.MethodsCDH1variant classification specifications were modified based on updated genetic testing clinical criteria, new recommendations from ClinGen and expert knowledge from ongoingCDH1variant curations. TheCDH1VCEP reviewed 273 variants using updatedCDH1specifications and incorporated published and unpublished data provided by diagnostic laboratories.ResultsUpdatedCDH1-specific interpretation guidelines include 11 major modifications since the initial specifications from 2018. Using the refined guidelines, 97% (36 of 37) of variants with ClinVar conflicting interpretations were resolved to benign, likely benign, likely pathogenic or pathogenic, and 35% (15 of 43) of VUS were resolved to benign or likely benign. Overall, 88% (239 of 273) of curated variants had non-VUS classifications. To date, variants classified as pathogenic are either nonsense, frameshift, splicing, or affecting the translation initiation codon, and the only missense variants classified as pathogenic or likely pathogenic have been shown to affect splicing.ConclusionsThe development and evolution ofCDH1-specific criteria by the expert panel resulted in decreased uncertain and conflicting interpretations of variants in this clinically actionable gene, which can ultimately lead to more effective clinical management recommendations.
Published: 2023

37. Noncoding Aberrations in Mismatch Repair Genes Underlie a Substantial Part of the Missing Heritability in Lynch Syndrome

Author: Iris B.A.W. Te Paske, Arjen R. Mensenkamp, Kornelia Neveling, Nicoline Hoogerbrugge, Marjolijn J.L. Ligtenberg, Richarda M. De Voer, Stéphanie Baert-Desurmont, Kathleen B.M. Claes, Kim de Leeneer, Lisa Elze, Simone van den Heuvel, Rachel S. van der Post, Yvonne van Twuijver, Tjakko J. van Ham, Anja Wagner, Mirjam M. de Jong, Edward M. Leter, Maartje Nielsen, MUMC+: DA KG Polikliniek (9), and RS: FHML non-thematic output
Subjects: Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Hereditary Nonpolyposis/diagnosis, Hepatology, Gastroenterology, Biology and Life Sciences, DNA Mismatch Repair/genetics, DNA Mismatch Repair, Colorectal Neoplasms, Hereditary Nonpolyposis, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Medicine and Health Sciences, Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis, Humans, Colorectal Neoplasms
Abstract: Contains fulltext : 288219.pdf (Publisher’s version ) (Open Access)
Published: 2022

38. Clinical applicability of the Polygenic Risk Score for breast cancer risk prediction in familial cases

Author: Lakeman, Inge MM, Rodríguez-Girondo, Mar DM, Lee, Andrew, Celosse, Nandi, Braspenning, Merel E, Van Engelen, Klaartje, Van De Beek, Irma, Van Der Hout, Annemiek H, Gómez García, Encarna B, Mensenkamp, Arjen R, Ausems, Margreet GEM, Hooning, Maartje J, Adank, Muriel A, Hollestelle, Antoinette, Schmidt, Marjanka K, Van Asperen, Christi J, Devilee, Peter, Human genetics, Cancer Center Amsterdam, Medical Oncology, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Lakeman, Inge MM [0000-0002-2990-7154], Lee, Andrew [0000-0003-0677-0252], Mensenkamp, Arjen R [0000-0003-3805-877X], Devilee, Peter [0000-0002-8023-2009], and Apollo - University of Cambridge Repository
Subjects: Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Polymorphism, Genetic, MODELS, LOCI, WOMEN, Breast Neoplasms, VARIANTS, Medical Oncology, Risk Assessment, PANEL, SDG 3 - Good Health and Well-being, Genetic, Risk Factors, Genetics, Humans, Female, Genetic Predisposition to Disease, Polymorphism, Cancer genetics, Genetics (clinical), Retrospective Studies
Abstract: Peer reviewed: True, Acknowledgements: We would like to thank Mary Velthuizen (University Medical Center Utrecht), J Margriet Collée (Erasmus Medical Center Rotterdam), Wendy Prager-van den Smissen (Erasmus Medical Center Rotterdam), Daoud Ait Moha (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital), Jan C Oosterwijk (University Medical Center Groningen), Janet R Vos (Radboud University Medical Center), Jeroen FJ Laros (Leiden University Medical Center) and Adri JM Krol (Leiden University Medical Center) for collecting and converting the pedigree files of the included families., BACKGROUND: Common low-risk variants are presently not used to guide clinical management of familial breast cancer (BC). We explored the additive impact of a 313-variant-based Polygenic Risk Score (PRS313) relative to standard gene testing in non-BRCA1/2 Dutch BC families. METHODS: We included 3918 BC cases from 3492 Dutch non-BRCA1/2 BC families and 3474 Dutch population controls. The association of the standardised PRS313 with BC was estimated using a logistic regression model, adjusted for pedigree-based family history. Family history of the controls was imputed for this analysis. SEs were corrected to account for relatedness of individuals. Using the BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) V.5 model, lifetime risks were retrospectively calculated with and without individual PRS313. For 2586 cases and 2584 controls, the carrier status of pathogenic variants (PVs) in ATM, CHEK2 and PALB2 was known. RESULTS: The family history-adjusted PRS313 was significantly associated with BC (per SD OR=1.97, 95% CI 1.84 to 2.11). Including the PRS313 in BOADICEA family-based risk prediction would have changed screening recommendations in up to 27%, 36% and 34% of cases according to BC screening guidelines from the USA, UK and the Netherlands (National Comprehensive Cancer Network, National Institute for Health and Care Excellence, and Netherlands Comprehensive Cancer Organisation), respectively. For the population controls, without information on family history, this was up to 39%, 44% and 58%, respectively. Among carriers of PVs in known moderate BC susceptibility genes, the PRS313 had the largest impact for CHEK2 and ATM. CONCLUSIONS: Our results support the application of the PRS313 in risk prediction for genetically uninformative BC families and families with a PV in moderate BC risk genes.
Published: 2023
Full Text: View/download PDF

39. Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study

Author: Noguès, Catherine, Laborde, Lilian, Pontois, Pauline, Breysse, Emanuelle, Berline, Margot, Stoppa-Lyonnet, Dominique, Gauthier-Villars, Marion, Buecher, Bruno, Colas, Chrystelle, Caron, Olivier, Mouret-Fourme, Emmanuelle, Saule, Claire, Fricker, Jean-Pierre, Lasset, Christine, Bonadona, Valérie, Dussard, Sophie, Berthet, Pascaline, Faivre, Laurence, Luporsi, Elisabeth, Mari, Véronique, Gladieff, Laurence, Gesta, Paul, Chieze-Valéro, Stéphanie, Moretta, Jessica, Sobol, Hagay, Eisinger, François, Popovici, Cornel, Longy, Michel, Grivelli, Louise, Soubrier, Florent, Benusiglio, Patrick, Coupier, Isabelle, Pujol, Pascal, Corsini, Carole, Morin-Meschin, Marie-Emmanuelle, Lortholary, Alain, Adenis, Claude, Maillez, Audrey, Nguyen, Tan Dat, Delnatte, Capucine, Abadie, Caroline, Tinat, Julie, Tennevet, Isabelle, Maugard, Christine, Bignon, Yves-Jean, Gay Bellile, Mathilde, Penet, Clotilde, Dreyfus, Hélène, Cohen-Haguenauer, Odile, Gilbert, Brigitte, Venat-Bouvet, Laurence, Leroux, Dominique, Legrand, Clémentine, Zattara-Cannoni, Hélène, Layet, Valérie, Lacaze, Elodie, Fert-Ferrer, Sandra, Bera, Odile, Gilbert-Dussardier, Brigitte, Tougeron, David, Lallaoui, Hakima, Rookus, M.A., Hogervorst, F.B.L., van Leeuwen, F.E., Adank, M.A., Schmidt, M.K., Jenner, D.J., Collée, J.M., van den Ouweland, A.M.W., Hooning, M.J., Boere, I.A., van Asperen, C.J., Devilee, P., van der Luijt, R.B., van Cronenburg, T.C.T.E.F., Wevers, M.R., Mensenkamp, A.R., Ausems, M.G.E.M., Koudijs, M.J., van de Beek, I., van Engelen, K., Gille, J.J.P., Gómez García, E.B., Blok, M.J., de Boer, M., Berger, L.P.V., van der Hout, A.H., Mourits, M.J.E., de Bock, G.H., Siesling, S., Verloop, J., van den Broek, E.C., Schrijver, Lieske H., Antoniou, Antonis C., Olsson, Håkan, Mooij, Thea M., Roos-Blom, Marie-José, Azarang, Leyla, Adlard, Julian, Ahmed, Munaza, Barrowdale, Daniel, Davidson, Rosemarie, Donaldson, Alan, Eeles, Ros, Evans, D. Gareth, Frost, Debra, Henderson, Alex, Izatt, Louise, Ong, Kai-Ren, van Engelen, Klaartje, Jager, Agnes, Menko, Fred H., Mourits, Marian J.E., Singer, Christian F., Tan, Yen Y., Foretova, Lenka, Navratilova, Marie, Schmutzler, Rita K., Ellberg, Carolina, Gerdes, Anne-Marie, Caldes, Trinidad, Simard, Jacques, Olah, Edith, Jakubowska, Anna, Rantala, Johanna, Osorio, Ana, Hopper, John L., Phillips, Kelly-Anne, Milne, Roger L., Beth Terry, Mary, Engel, Christoph, Kast, Karin, Goldgar, David E., van Leeuwen, Flora E., Easton, Douglas F., Andrieu, Nadine, and Rookus, Matti A.
Published: 2021
Full Text: View/download PDF

40. SNP association study in PMS2-associated Lynch syndrome

Author: ten Broeke, Sanne W., Elsayed, Fadwa A., Pagan, Lisa, Olderode-Berends, Maran J. W., Garcia, Encarna Gomez, Gille, Hans J. P., van Hest, Liselot P., Letteboer, Tom G. W., van der Kolk, Lizet E., Mensenkamp, Arjen R., van Os, Theo A., Spruijt, Liesbeth, Redeker, Bert J. W., Suerink, Manon, Vos, Yvonne J., Wagner, Anja, Wijnen, Juul T., Steyerberg, E. W., Tops, Carli M. J., van Wezel, Tom, and Nielsen, Maartje
Published: 2018
Full Text: View/download PDF

41. The association between cancer family history and ovarian cancer risk in BRCA1/2 mutation carriers: can it be explained by the mutation position?

Author: Teixeira, Natalia, van der Hout, Annemieke, Oosterwijk, Jan C., Vos, Janet R., HEBON, Devilee, Peter, van Engelen, Klaartje, Meijers-Heijboer, Hanne, van der Luijt, Rob B., Kriege, Mieke, Mensenkamp, Arjen R., Rookus, Matti A., van Roozendaal, Kees E., Mourits, Marian J. E., and de Bock, Geertruida H.
Published: 2018
Full Text: View/download PDF

42. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

Author: Hollestelle, Antoinette, van der Baan, Frederieke H., Berchuck, Andrew, Johnatty, Sharon E., Aben, Katja K., Agnarsson, Bjarni A., Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Antoniou, Antonis C., Apicella, Carmel, Arndt, Volker, Arnold, Norbert, Arun, Banu K., Arver, Brita, Ashworth, Alan, Baglietto, Laura, Balleine, Rosemary, Bandera, Elisa V., Barrowdale, Daniel, Bean, Yukie T., Beckmann, Lars, Beckmann, Matthias W., Benitez, Javier, Berger, Andreas, Berger, Raanan, Beuselinck, Benoit, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Bogdanova, Natalia V., Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Brand, Judith S., Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Brüning, Thomas, Budzilowska, Agnieszka, Bunker, Clareann H., Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Caligo, Maria A., Campbell, Ian, Carter, Jonathan, Chang-Claude, Jenny, Chanock, Stephen J., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Linda S., Couch, Fergus J., Cox, Angela, Cramer, Daniel, Cross, Simon S., Cunningham, Julie M., Cybulski, Cezary, Czene, Kamila, Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, de la Hoya, Miguel, deFazio, Anna, Dennis, Joseph, Devilee, Peter, Dicks, Ed M., Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Silva, Isabel Dos Santos, du Bois, Andreas, Dumont, Martine, Dunning, Alison M., Duran, Mercedes, Easton, Douglas F., Eccles, Diana, Edwards, Robert P., Ehrencrona, Hans, Ejlertsen, Bent, Ekici, Arif B., Ellis, Steve D., Engel, Christoph, Eriksson, Mikael, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Fontaine, Annette, Fortuzzi, Stefano, Fostira, Florentia, Fridley, Brooke L., Friebel, Tara, Friedman, Eitan, Friel, Grace, Frost, Debra, Garber, Judy, García-Closas, Montserrat, Gayther, Simon A., Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Giles, Graham G., Glasspool, Rosalind, Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Gore, Martin, Greene, Mark H., Grip, Mervi, Gronwald, Jacek, Gschwantler Kaulich, Daphne, Guénel, Pascal, Guzman, Starr R., Haeberle, Lothar, Haiman, Christopher A., Hall, Per, Halverson, Sandra L., Hamann, Ute, Hansen, Thomas V.O., Harter, Philipp, Hartikainen, Jaana M., Healey, Sue, Hein, Alexander, Heitz, Florian, Henderson, Brian E., Herzog, Josef, T Hildebrandt, Michelle A., Høgdall, Claus K., Høgdall, Estrid, Hogervorst, Frans B.L., Hopper, John L., Humphreys, Keith, Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, Janavicius, Ramunas, Jaworska, Katarzyna, Jensen, Allan, Jensen, Uffe Birk, Johnson, Nichola, Jukkola-Vuorinen, Arja, Kabisch, Maria, Karlan, Beth Y., Kataja, Vesa, Kauff, Noah, Kelemen, Linda E., Kerin, Michael J., Kiemeney, Lambertus A., Kjaer, Susanne K., Knight, Julia A., Knol-Bout, Jacoba P., Konstantopoulou, Irene, Kosma, Veli-Matti, Krakstad, Camilla, Kristensen, Vessela, Kuchenbaecker, Karoline B., Kupryjanczyk, Jolanta, Laitman, Yael, Lambrechts, Diether, Lambrechts, Sandrina, Larson, Melissa C., Lasa, Adriana, Laurent-Puig, Pierre, Lazaro, Conxi, Le, Nhu D., Le Marchand, Loic, Leminen, Arto, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Liang, Dong, Lindblom, Annika, Lindor, Noralane, Lissowska, Jolanta, Long, Jirong, Lu, Karen H., Lubinski, Jan, Lundvall, Lene, Lurie, Galina, Mai, Phuong L., Mannermaa, Arto, Margolin, Sara, Mariette, Frederique, Marme, Frederik, Martens, John W.M., Massuger, Leon F.A.G., Maugard, Christine, Mazoyer, Sylvie, McGuffog, Lesley, McGuire, Valerie, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menegaux, Florence, Menéndez, Primitiva, Menkiszak, Janusz, Menon, Usha, Mensenkamp, Arjen R., Miller, Nicola, Milne, Roger L., Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Müller, Heiko, Mulligan, Anna Marie, Muranen, Taru A., Narod, Steven A., Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Nielsen, Finn C., Nielsen, Sune F., Nordestgaard, Børge G., Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olson, Sara H., Oosterwijk, Jan C., Orlow, Irene, Orr, Nick, Orsulic, Sandra, Osorio, Ana, Ottini, Laura, Paul, James, Pearce, Celeste L., Pedersen, Inge Sokilde, Peissel, Bernard, Pejovic, Tanja, Pelttari, Liisa M., Perkins, Jo, Permuth-Wey, Jenny, Peterlongo, Paolo, Peto, Julian, Phelan, Catherine M., Phillips, Kelly-Anne, Piedmonte, Marion, Pike, Malcolm C., Platte, Radka, Plisiecka-Halasa, Joanna, Poole, Elizabeth M., Poppe, Bruce, Pylkäs, Katri, Radice, Paolo, Ramus, Susan J., Rebbeck, Timothy R., Reed, Malcolm W.R., Rennert, Gad, Risch, Harvey A., Robson, Mark, Rodriguez, Gustavo C., Romero, Atocha, Rossing, Mary Anne, Rothstein, Joseph H., Rudolph, Anja, Runnebaum, Ingo, Salani, Ritu, Salvesen, Helga B., Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schrauder, Michael G., Schumacher, Fredrick, Schwaab, Ira, Scuvera, Giulietta, Sellers, Thomas A., Severi, Gianluca, Seynaeve, Caroline M., Shah, Mitul, Shrubsole, Martha, Siddiqui, Nadeem, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sinilnikova, Olga M., Smeets, Dominiek, Sohn, Christof, Soller, Maria, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stegmaier, Christa, Stoppa-Lyonnet, Dominique, Sucheston, Lara, Swerdlow, Anthony, Tangen, Ingvild L., Tea, Muy-Kheng, Teixeira, Manuel R., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Tihomirova, Laima, Tischkowitz, Marc, Toland, Amanda Ewart, Tollenaar, Rob A.E.M., Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tsimiklis, Helen, Tung, Nadine, Tworoger, Shelley S., Tyrer, Jonathan P., Vachon, Celine M., Van 't Veer, Laura J., van Altena, Anne M., Van Asperen, C.J., van den Berg, David, van den Ouweland, Ans M.W., van Doorn, Helena C., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vergote, Ignace, Verhoef, Senno, Vierkant, Robert A., Vijai, Joseph, Vitonis, Allison F., von Wachenfeldt, Anna, Walsh, Christine, Wang, Qin, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weischer, Maren, Weitzel, Jeffrey N., Weltens, Caroline, Wentzensen, Nicolas, Whittemore, Alice S., Wilkens, Lynne R., Winqvist, Robert, Wu, Anna H., Wu, Xifeng, Yang, Hannah P., Zaffaroni, Daniela, Pilar Zamora, M., Zheng, Wei, Ziogas, Argyrios, Chenevix-Trench, Georgia, Pharoah, Paul D.P., Rookus, Matti A., Hooning, Maartje J., and Goode, Ellen L.
Published: 2016
Full Text: View/download PDF

43. The effect of genotypes and parent of origin on cancer risk and age of cancer development in PMS2 mutation carriers

Author: Suerink, Manon, van der Klift, Heleen M., ten Broeke, Sanne W., Dekkers, Olaf M., Bernstein, Inge, Capellá Munar, Gabriel, Gomez Garcia, Encarna, Hoogerbrugge, Nicoline, Letteboer, Tom G.W., Menko, Fred H., Lindblom, Annika, Mensenkamp, Arjen, Moller, Pal, van Os, Theo A., Rahner, Nils, Redeker, Bert J.W., Olderode, Maran, Spruijt, Liesbeth, Vos, Yvonne J., Wagner, Anja, Morreau, Hans, Hes, Frederik J., Vasen, Hans F.A., Tops, Carli M., Wijnen, Juul T., and Nielsen, Maartje
Published: 2016
Full Text: View/download PDF

44. Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Author: Arts, Peer, Simons, Annet, AlZahrani, Mofareh S., Yilmaz, Elanur, AlIdrissi, Eman, van Aerde, Koen J., Alenezi, Njood, AlGhamdi, Hamza A., AlJubab, Hadeel A., Al-Hussaini, Abdulrahman A., AlManjomi, Fahad, Alsaad, Alaa B., Alsaleem, Badr, Andijani, Abdulrahman A., Asery, Ali, Ballourah, Walid, Bleeker-Rovers, Chantal P., van Deuren, Marcel, van der Flier, Michiel, Gerkes, Erica H., Gilissen, Christian, Habazi, Murad K., Hehir-Kwa, Jayne Y., Henriet, Stefanie S., Hoppenreijs, Esther P., Hortillosa, Sarah, Kerkhofs, Chantal H., Keski-Filppula, Riikka, Lelieveld, Stefan H., Lone, Khurram, MacKenzie, Marius A., Mensenkamp, Arjen R., Moilanen, Jukka, Nelen, Marcel, ten Oever, Jaap, Potjewijd, Judith, van Paassen, Pieter, Schuurs-Hoeijmakers, Janneke H. M., Simon, Anna, Stokowy, Tomasz, van de Vorst, Maartje, Vreeburg, Maaike, Wagner, Anja, van Well, Gijs T. J., Zafeiropoulou, Dimitra, Zonneveld-Huijssoon, Evelien, Veltman, Joris A., van Zelst-Stams, Wendy A. G., Faqeih, Eissa A., van de Veerdonk, Frank L., Netea, Mihai G., and Hoischen, Alexander
Published: 2019
Full Text: View/download PDF

45. Cancer risks by sex and variant type in PTEN hamartoma tumor syndrome.

Author: Hendricks, L.A.J., Hoogerbrugge, N., Mensenkamp, A.R., Brunet, J., Lleuger-Pujol, R., Høberg-Vetti, H., Tveit Haavind, M., Innella, G., Turchetti, D., Aretz, S., Spier, I., Tischkowitz, M., Jahn, A., Links, T.P., Olderode-Berends, M.J., Blatnik, A., Leter, E.M., Evans, D.G., Woodward, E.R., Steinke-Lange, V., Anastasiadou, V.C., Colas, C., Villy, M.C., Benusiglio, P.R., Gerasimenko, A., Barili, V., Branchaud, M., Houdayer, C., Tesi, B., Yazicioglu, M.O., Post, R.S. van der, Schuurs-Hoeijmakers, J.H.M., Vos, J.R., Hendricks, L.A.J., Hoogerbrugge, N., Mensenkamp, A.R., Brunet, J., Lleuger-Pujol, R., Høberg-Vetti, H., Tveit Haavind, M., Innella, G., Turchetti, D., Aretz, S., Spier, I., Tischkowitz, M., Jahn, A., Links, T.P., Olderode-Berends, M.J., Blatnik, A., Leter, E.M., Evans, D.G., Woodward, E.R., Steinke-Lange, V., Anastasiadou, V.C., Colas, C., Villy, M.C., Benusiglio, P.R., Gerasimenko, A., Barili, V., Branchaud, M., Houdayer, C., Tesi, B., Yazicioglu, M.O., Post, R.S. van der, Schuurs-Hoeijmakers, J.H.M., and Vos, J.R.
Abstract: Item does not contain fulltext, BACKGROUND: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks. METHODS: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses. RESULTS: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%. CONCLUSIONS: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.
Published: 2023

46. Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines.

Author: Luo, X., Maciaszek, J.L., Thompson, B.A., Leong, H.S., Dixon, K., Sousa, S., Anderson, M., Roberts, M.E., Lee, K., Spurdle, A.B., Mensenkamp, A.R., Brannan, T., Pardo, C., Zhang, L., Pesaran, T., Wei, S., Fasaye, G.A., Kesserwan, C., Shirts, B.H., Davis, J.L., Oliveira, C. de, Plon, S.E., Schrader, Kasmintan A., Karam, R., Luo, X., Maciaszek, J.L., Thompson, B.A., Leong, H.S., Dixon, K., Sousa, S., Anderson, M., Roberts, M.E., Lee, K., Spurdle, A.B., Mensenkamp, A.R., Brannan, T., Pardo, C., Zhang, L., Pesaran, T., Wei, S., Fasaye, G.A., Kesserwan, C., Shirts, B.H., Davis, J.L., Oliveira, C. de, Plon, S.E., Schrader, Kasmintan A., and Karam, R.
Abstract: 01 juni 2023, Item does not contain fulltext, BACKGROUND: Germline pathogenic variants in CDH1 are associated with increased risk of diffuse gastric cancer and lobular breast cancer. Risk reduction strategies include consideration of prophylactic surgery, thereby making accurate interpretation of germline CDH1 variants critical for physicians deciding on these procedures. The Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel (VCEP) developed specifications for CDH1 variant curation with a goal to resolve variants of uncertain significance (VUS) and with ClinVar conflicting interpretations and continues to update these specifications. METHODS: CDH1 variant classification specifications were modified based on updated genetic testing clinical criteria, new recommendations from ClinGen and expert knowledge from ongoing CDH1 variant curations. The CDH1 VCEP reviewed 273 variants using updated CDH1 specifications and incorporated published and unpublished data provided by diagnostic laboratories. RESULTS: Updated CDH1-specific interpretation guidelines include 11 major modifications since the initial specifications from 2018. Using the refined guidelines, 97% (36 of 37) of variants with ClinVar conflicting interpretations were resolved to benign, likely benign, likely pathogenic or pathogenic, and 35% (15 of 43) of VUS were resolved to benign or likely benign. Overall, 88% (239 of 273) of curated variants had non-VUS classifications. To date, variants classified as pathogenic are either nonsense, frameshift, splicing, or affecting the translation initiation codon, and the only missense variants classified as pathogenic or likely pathogenic have been shown to affect splicing. CONCLUSIONS: The development and evolution of CDH1-specific criteria by the expert panel resulted in decreased uncertain and conflicting interpretations of variants in this clinically actionable gene, which can ultimately lead to more effective clinical management recommendations.
Published: 2023

47. PRDM10 directs FLCN expression in a novel disorder overlapping with Birt-Hogg-Dubé syndrome and familial lipomatosis.

Author: Beek, I. van de, Glykofridis, I.E., Oosterwijk, Jan C., Akker, P.C. van den, Diercks, G.F., Bolling, M.C., Waisfisz, Q., Mensenkamp, A.R., Balk, J.A., Zwart, R. van der, Postma, A.V., Meijers-Heijboer, H.E., Moorselaar, R.J.A. van, Wolthuis, R.M.F., Houweling, A.C., Beek, I. van de, Glykofridis, I.E., Oosterwijk, Jan C., Akker, P.C. van den, Diercks, G.F., Bolling, M.C., Waisfisz, Q., Mensenkamp, A.R., Balk, J.A., Zwart, R. van der, Postma, A.V., Meijers-Heijboer, H.E., Moorselaar, R.J.A. van, Wolthuis, R.M.F., and Houweling, A.C.
Abstract: Item does not contain fulltext, Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder characterized by fibrofolliculomas, pulmonary cysts, pneumothoraces and renal cell carcinomas. Here, we reveal a novel hereditary disorder in a family with skin and mucosal lesions, extensive lipomatosis and renal cell carcinomas. The proband was initially diagnosed with BHD based on the presence of fibrofolliculomas, but no pathogenic germline variant was detected in FLCN, the gene associated with BHD. By whole exome sequencing we identified a heterozygous missense variant (p.(Cys677Tyr)) in a zinc-finger encoding domain of the PRDM10 gene which co-segregated with the phenotype in the family. We show that PRDM10Cys677Tyr loses affinity for a regulatory binding motif in the FLCN promoter, abrogating cellular FLCN mRNA and protein levels. Overexpressing inducible PRDM10Cys677Tyr in renal epithelial cells altered the transcription of multiple genes, showing overlap but also differences with the effects of knocking out FLCN. We propose that PRDM10 controls an extensive gene program and acts as a critical regulator of FLCN gene transcription in human cells. The germline variant PRDM10Cys677Tyr curtails cellular folliculin expression and underlies a distinguishable syndrome characterized by extensive lipomatosis, fibrofolliculomas and renal cell carcinomas.
Published: 2023

48. Microsatellite instability in noncolorectal and nonendometrial malignancies in patients with Lynch syndrome.

Author: Elze, L., Post, R.S. van der, Vos, J.R., Mensenkamp, A.R., Hullu, M.S.C. de, Nagtegaal, I.D., Hoogerbrugge, N., Voer, R.M. de, Ligtenberg, M.J.L., Elze, L., Post, R.S. van der, Vos, J.R., Mensenkamp, A.R., Hullu, M.S.C. de, Nagtegaal, I.D., Hoogerbrugge, N., Voer, R.M. de, and Ligtenberg, M.J.L.
Abstract: Contains fulltext : 294522.pdf (Publisher’s version ) (Open Access), BACKGROUND: Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics. METHODS: We retrieved the full tumor history of a historical clinic-based cohort of 1745 individuals with Lynch syndrome and calculated the standardized incidence ratio for all tumor types. MSI status, somatic second hit alterations, and immunohistochemistry-based MMR status were analyzed in 236 noncolorectal and nonendometrial malignant tumors. RESULTS: In individuals with Lynch syndrome MSI-H/dMMR occurred both in Lynch-spectrum and in non-Lynch-spectrum malignancies (85% vs 37%, P < .01). MSI-H/dMMR malignancies were found in nearly all non-Lynch-spectrum tumor types. Almost all breast carcinomas had medullary features, and most of them were MSI-H/dMMR. Breast carcinoma with medullary features were shown to be associated with Lynch syndrome (standardized incidence ratio = 38.8, 95% confidence interval = 16.7 to 76.5). CONCLUSIONS: In individuals with Lynch syndrome, MSI-H/dMMR occurs in more than one-half of the malignancies other than colorectal and endometrial carcinomas, including tumor types without increased incidence. The Lynch-spectrum tumors should be expanded to breast carcinomas with medullary features. All malignancies in patients with Lynch syndrome, independent of subtype, should be tested for MSI-H/dMMR in case therapy with immune checkpoint inhibitors is considered. Moreover, Lynch syndrome should be considered an underlying cause of all MSI-H/dMMR malignancies other than colorectal and endometrial carcinomas.
Published: 2023

49. Clinical applicability of the Polygenic Risk Score for breast cancer risk prediction in familial cases

Author: Lakeman, I.M.M., Rodríguez-Girondo, M.D.M., Lee, A, Celosse, N., Braspenning, M.E., Engelen, K. van, Beek, I. van de, Hout, A.H. van der, Gómez García, E., Mensenkamp, A.R., Ausems, M.G.E.M., Hooning, M.J., Adank, M.A., Hollestelle, A., Schmidt, M.K., Asperen, C.J. van, Devilee, P., Lakeman, I.M.M., Rodríguez-Girondo, M.D.M., Lee, A, Celosse, N., Braspenning, M.E., Engelen, K. van, Beek, I. van de, Hout, A.H. van der, Gómez García, E., Mensenkamp, A.R., Ausems, M.G.E.M., Hooning, M.J., Adank, M.A., Hollestelle, A., Schmidt, M.K., Asperen, C.J. van, and Devilee, P.
Abstract: Item does not contain fulltext, BACKGROUND: Common low-risk variants are presently not used to guide clinical management of familial breast cancer (BC). We explored the additive impact of a 313-variant-based Polygenic Risk Score (PRS(313)) relative to standard gene testing in non-BRCA1/2 Dutch BC families. METHODS: We included 3918 BC cases from 3492 Dutch non-BRCA1/2 BC families and 3474 Dutch population controls. The association of the standardised PRS(313) with BC was estimated using a logistic regression model, adjusted for pedigree-based family history. Family history of the controls was imputed for this analysis. SEs were corrected to account for relatedness of individuals. Using the BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) V.5 model, lifetime risks were retrospectively calculated with and without individual PRS(313). For 2586 cases and 2584 controls, the carrier status of pathogenic variants (PVs) in ATM, CHEK2 and PALB2 was known. RESULTS: The family history-adjusted PRS(313) was significantly associated with BC (per SD OR=1.97, 95% CI 1.84 to 2.11). Including the PRS(313) in BOADICEA family-based risk prediction would have changed screening recommendations in up to 27%, 36% and 34% of cases according to BC screening guidelines from the USA, UK and the Netherlands (National Comprehensive Cancer Network, National Institute for Health and Care Excellence, and Netherlands Comprehensive Cancer Organisation), respectively. For the population controls, without information on family history, this was up to 39%, 44% and 58%, respectively. Among carriers of PVs in known moderate BC susceptibility genes, the PRS(313) had the largest impact for CHEK2 and ATM. CONCLUSIONS: Our results support the application of the PRS(313) in risk prediction for genetically uninformative BC families and families with a PV in moderate BC risk genes.
Published: 2023

50. Cancer risks by sex and variant type in PTEN hamartoma tumor syndrome

Author: Hendricks, Linda A.J., Hoogerbrugge, Nicoline, Mensenkamp, Arjen R., Brunet, Joan, Lleuger-Pujol, Roser, Høberg-Vetti, Hildegunn, Haavind, Marianne Tveit, Innella, Giovanni, Turchetti, Daniela, Aretz, Stefan, Spier, Isabel, Tischkowitz, Marc, Jahn, Arne, Links, Thera P., Olderode-Berends, Maran J.W., Blatnik, Ana, Leter, Edward M., Evans, D. Gareth, Woodward, Emma R., Steinke-Lange, Verena, Anastasiadou, Violetta C., Colas, Chrystelle, Villy, Marie Charlotte, Benusiglio, Patrick R., Gerasimenko, Anna, Barili, Valeria, Branchaud, Maud, Houdayer, Claude, Tesi, Bianca, Yazicioglu, M. Omer, van der Post, Rachel S., Schuurs-Hoeijmakers, Janneke H.M., Vos, Janet R., Duijkers, Floor, van Ierland, Yvette, Hendricks, Linda A.J., Hoogerbrugge, Nicoline, Mensenkamp, Arjen R., Brunet, Joan, Lleuger-Pujol, Roser, Høberg-Vetti, Hildegunn, Haavind, Marianne Tveit, Innella, Giovanni, Turchetti, Daniela, Aretz, Stefan, Spier, Isabel, Tischkowitz, Marc, Jahn, Arne, Links, Thera P., Olderode-Berends, Maran J.W., Blatnik, Ana, Leter, Edward M., Evans, D. Gareth, Woodward, Emma R., Steinke-Lange, Verena, Anastasiadou, Violetta C., Colas, Chrystelle, Villy, Marie Charlotte, Benusiglio, Patrick R., Gerasimenko, Anna, Barili, Valeria, Branchaud, Maud, Houdayer, Claude, Tesi, Bianca, Yazicioglu, M. Omer, van der Post, Rachel S., Schuurs-Hoeijmakers, Janneke H.M., Vos, Janet R., Duijkers, Floor, and van Ierland, Yvette
Abstract: Background: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks. Methods: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses. Results: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range ¼ 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] ¼ 43.0% to 66.4%) to 75.8% (95% CI ¼ 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI ¼ 2.1% to 18.6%) to 22.1% (95% CI ¼ 11.6% to 39.6%) and TC risks from 8.9% (95% CI ¼ 5.1% to 15.3%) to 20.5% (95% CI ¼ 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%. Conclusions: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management.
Published: 2023

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

953 results on '"Mensenkamp A."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources