A5053853285- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Cutaneous Melanoma Detection and Management
- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Metabolism and Genetic Disorders
- Chromatin Remodeling and Cancer
- Genomic variations and chromosomal abnormalities
- Genetic factors in colorectal cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Hormonal Regulation and Hypertension
- Skin Protection and Aging
- Prenatal Screening and Diagnostics
- Adrenal and Paraganglionic Tumors
- Neuroendocrine Tumor Research Advances
- Ethics in Clinical Research
- Colorectal Cancer Screening and Detection
- Pituitary Gland Disorders and Treatments
- Multiple and Secondary Primary Cancers
- melanin and skin pigmentation
- Genetics and Neurodevelopmental Disorders
- Ocular Oncology and Treatments
- PARP inhibition in cancer therapy
- Immunotherapy and Immune Responses
Leiden University Medical Center
2015-2025
Leiden University
2017-2024
Isala
2012-2016
Merck Serono (Switzerland)
2016
Bayer (United States)
2016
Merck Serono (Italy)
2016
Roche (Switzerland)
2016
Sanofi (France)
2016
Amgen (United States)
2016
Sanofi (Mexico)
2016
Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play role in the development of PDAC 3% to 5% all patients. Surveillance high-risk groups, may facilitate detection at an early stage. The aim this study was assess whether surveillance aids early-stage or precursor lesions (PRLs) and improves Patients Methods Screening outcomes were collected from three European centers that conduct prospective screening groups including families with clustering...
Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield outcomes 20 years prospective a large cohort germline pathogenic variants (PVs) CDKN2A.Prospectively collected data were analyzed from participating surveillance. Surveillance consisted annual magnetic resonance imaging cholangiopancreatography optional endoscopic ultrasound.Three hundred...
Recent pancreatic cancer surveillance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes ductal adenocarcinoma (PDAC) in patients with a CDKN2A/p16 pathogenic variant diagnosed under are better as compared PDAC outside surveillance.In propensity score matched cohort using data from the Netherlands Cancer Registry, we resectability, stage, and survival between non-surveillance PDAC. Survival analyses were adjusted for potential...
PURPOSE Guidelines recommend germline genetic testing (GT) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aims to evaluate the utilization and outcomes of multigene panel GT in PDAC. METHODS retrospective, multisite included PDAC diagnosed between May 2018 August 2020 at Mayo Clinic Arizona, Florida, Minnesota. Discussion, uptake, were compared before (May 1, 2018-May 2019) after (August 2019-August 2020) guideline update, accounting a transition period. RESULTS The...
Pancreatic ductal adenocarcinoma (PDAC) surveillance programs are currently offered to high-risk individuals aiming detect precursor lesions or PDAC at an early stage. We assessed differences in frequency and behavior of between two groups.Individuals with a p16-Leiden germline mutation (N = 116; median age 54 years) from familial pancreatic cancer (FPC) families 125; 47 were annual by MRI magnetic resonance cholangiopancreatography (MRCP) without endoscopic ultrasound (EUS) for period 34...
Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause BAP1-tumor predisposition syndrome (BAP1-TPDS, OMIM 614327). BAP1-TPDS is associated with an increased risk of developing uveal melanoma (UM), cutaneous (CM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), meningioma, cholangiocarcinoma, multiple non-melanoma skin cancers, and BAP1-inactivated nevi. Because this risk, it important to identify patients BAP1-TPDS. The tumors are treated by different...
ABSTRACT Background Individuals with a germline CDKN2A pathogenic variant (PV) have an increased lifetime risk of melanoma and pancreatic cancer. It is unknown whether the PV impacts quality life (QoL). Therefore we aimed to assess QoL psychological distress in families affected by PV. Methods This cross‐sectional study included confirmed carriers those 50% likelihood carrying (at‐risk carriers) under cancer surveillance who were invited complete one‐time questionnaire. Both at‐risk are...
At the CDKN2A/B locus, three independent signals for type 2 diabetes risk are located in a noncoding region near CDKN2A. The disease-associated alleles have been implicated reduced β-cell function, but underlying mechanism remains elusive. In mice, β-cell–specific loss of Cdkn2a causes hyperplasia, while overexpression leads to diabetes, highlighting CDKN2A as candidate effector transcript. Rare loss-of-function mutations cause familial melanoma and offer opportunity determine impact...
Germline mutations in the major melanoma susceptibility gene CDKN2A explain genetic predisposition only 10-40% of melanoma-prone families. In our study we comprehensively characterized 488 cases from 451 non-CDKN2A/CDK4 families for 30 established and candidate genes using a custom-designed targeted panel approach. We identified (likely) pathogenic variants 18 (n = 3 BAP1, n 15 MITF p.E318K; diagnostic yield 4.0%). Among three BAP1-families, there were no reported diagnoses uveal or...
To improve the diagnostic value of fine-needle aspiration (FNA)-derived material, we perform targeted next-generation sequencing (NGS) in patients with a suspect lesion pancreas. The NGS analysis can lead to change treatment plan or supports inconclusive uncertain cytology results. We describe advantages using one particular patient recurrent pancreatic 7 years after resection ductal adenocarcinoma (PDAC). Our revealed presence presumed second primary cancer remnant, which led treatment:...
Constitutional mismatch repair deficiency ( CMMRD ) is a rare, recessively inherited childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the genes. The phenotype overlaps with that neurofibromatosis type 1 NF1 ), since many patients have multiple café‐au‐lait macules CALM and other signs, but no mutations. We report case healthy 6‐year‐old girl who fulfilled diagnostic criteria >6 freckling. Since molecular genetic testing was unable to confirm...
Background Pathogenic variants in the CDKN2A gene are generally associated with development of melanoma and pancreatic ductal adenocarcinoma (PDAC), but specific genotype-phenotype correlations might exist extent PDAC risk is not well established for many variants. Methods Using Dutch national familial database, we identified all families a pathogenic variant investigated occurrence within these families. We also estimated standardised incidence ratio lifetime carriers highly prevalent...
CREB-binding protein (CBP, encoded by CREBBP) and its paralog E1A-associated (p300, EP300) are involved in histone acetylation transcriptional regulation. Variants that produce a null allele or disrupt the catalytic domain of either cause Rubinstein-Taybi syndrome (RSTS), while pathogenic missense in-frame indel variants parts exons 30 31 phenotypes recently described as Menke-Hennekam (MKHK). To distinguish MKHK subtypes define their characteristics, molecular extended clinical data on 82...
Importance Knowledge about the prevalence and tumor types of CDKN2A -related melanoma-astrocytoma syndrome (MAS) is limited could improve disease recognition. Objective To estimate describe MAS. Design, Setting, Participants This retrospective cohort study analyzed all available MAS cases from medical centers in US (2 sites) Europe biomedical population genomic databases (UK Biobank [United Kingdom], Geisinger MyCode [US]) between January 1, 1976, December 31, 2020. Patients with germline...
The p16-Leiden founder mutation in the CDKN2A gene is most common cause of Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome Netherlands. Individuals with this are at increased risk for developing melanoma skin, as well pancreatic cancer. However, there a notable interfamilial variability occurrence cancer among families. We aimed to test whether previously identified genetic factors modify germline carriers. Seven cancer-associated SNPs were selected from literature and genotyped...
Objectives The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating pancreatic cancer surveillance. Materials and Methods High-risk with a CDKN2A/p16 germline pathogenic variant surveillance were included this study. Multivariable logistic regression was performed assess relationship between new-onset diabetes (NOD) ductal adenocarcinoma (PDAC). To quantify diagnostic performance NOD as marker for PDAC, receiver operating...
Abstract Individuals with a germline CDKN2A pathogenic variant (PV) have highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, preimplantation testing (PGT) in confirmed PV carriers individuals 50% (at-risk carriers) using one-time questionnaire. A total 537 were screened for eligibility, whom 208 366 (57%) (56% female, median age 54 years [IQR 46–63]) 39 171 (23%) at-risk (59% 26...
Background Several factors have been reported that influence the probability of a germline CDKN2A mutation in melanoma family. Our goal was to create scoring system estimate this probability, based on set clinical features present patient and his or her Methods Five their association with mutations were investigated training cohort 1227 Dutch families (13.7% mutation) using multivariate logistic regression. Predefined included number family members multiple primary melanomas, median age at...
Pancreatic cancer (PC) surveillance is currently offered to individuals with a genetic predisposition PC, but routinely used radiological screening modalities are not entirely reliable in detecting early-stage PC or its precursor lesions. We recently identified discriminating biomarker signature sporadic patient cohort. In this study, we investigated if protein profiling can accurately distinguish from non-PC pancreatic cohort of genetically predisposed individuals.Serum samples 66 CDKN2A...