A5006742484- Ocular Oncology and Treatments
- Cancer-related Molecular Pathways
- BRCA gene mutations in cancer
- Prenatal Screening and Diagnostics
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- Genetic factors in colorectal cancer
- Reproductive Health and Technologies
- Hedgehog Signaling Pathway Studies
- DNA Repair Mechanisms
- Childhood Cancer Survivors' Quality of Life
- Cancer, Hypoxia, and Metabolism
- Polyomavirus and related diseases
- Genomic variations and chromosomal abnormalities
- Genetic Associations and Epidemiology
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Cancer Risks and Factors
- Glioma Diagnosis and Treatment
- Ethics and Legal Issues in Pediatric Healthcare
- CRISPR and Genetic Engineering
- Pancreatic and Hepatic Oncology Research
- Renal and related cancers
- Histiocytic Disorders and Treatments
- Hemoglobinopathies and Related Disorders
Dutch Cancer Society
2024
Cancer Center Amsterdam
2024
Vrije Universiteit Amsterdam
2012-2023
Amsterdam University Medical Centers
2019-2023
Amsterdam UMC Location Vrije Universiteit Amsterdam
2008-2018
University of Amsterdam
2009-2015
University Medical Center
2008
University Hospital and Clinics
2008
The Netherlands Cancer Institute
2006
Retinoblastoma is a rare childhood cancer initiated by RB1 mutation or MYCN amplification, while additional alterations may be required for tumor development. However, the view on single nucleotide variants very limited. To better understand oncogenesis, we determined genomic landscape of retinoblastoma. We performed exome sequencing 71 retinoblastomas and matched blood DNA. Next, presence variants, copy number viruses. Aside from RB1, recurrent gene mutations were rare. Only limited...
Importance To improve diagnostics of cancer predisposition syndromes (CPSs) in children with cancer, it is essential to evaluate the effect CPS gene sequencing among all and compare genetic testing based on clinical selection. However, a reliable comparison difficult because recent reports phenotype-first approach large, unselected childhood cohorts are lacking. Objective describe national children’s center’s experience diagnosing CPSs before introducing routine next-generation sequencing....
Hereditary non-polyposis colorectal cancer is an autosomal dominant condition due to germline mutations in DNA-mismatch-repair genes, particular MLH1, MSH2 and MSH6. Here we describe the application of a novel technique for detection genomic deletions MLH1 MSH2. This method, called multiplex ligation-dependent probe amplification, quantitative PCR approach determine relative copy number each exon. Mutation screening genes was performed 126 families selected on basis clinical criteria...
<h3>Background</h3> Retinoblastoma (Rb) is a childhood cancer of the retina, commonly initiated by biallelic inactivation <i>RB1</i> gene. Knowledge presence heritable mutation can help in risk management and reproductive decision making. We report here on scanning unique nationwide cohort Rb patients from Netherlands. <h3>Methods</h3> From 1173 registered Dutch National Register until January 2013, 529 433 unrelated families could be included. was performed with different detection methods,...
Survivors of hereditary retinoblastoma have a high risk second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater malignancies in large cohort. We conducted retrospective cohort study 199 survivors documented mutation diagnosed between 1905 and 2005. In total, 44 developed malignancy after median follow-up 30.2 years (range 1.33-76.0). A significantly increased was observed among carriers one the 11 recurrent CGA>TGA...
Abstract Background Assessment of the clinical significance unclassified variants (UVs) identified in BRCA1 and BRCA2 is very important for genetic counselling. The analysis co-segregation variant with disease families a powerful tool classification these variants. Statistical methods have been described literature but are not always easy to apply diagnostic setting. Methods We developed an use method which calculates likelihood ratio (LR) UV being deleterious, penetrance as function age...
Unclassified variants (UVs) in the BRCA1/BRCA2 genes are a frequent problem counseling breast cancer and/or ovarian families. Information about family history is usually available, but has rarely been used to evaluate UVs. The aim of present study was identify which best combination clinical parameters that can predict whether UV deleterious, be for classification We developed logistic regression models with features distinguished positive control BRCA pathogenic (115 families) from negative...
Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of due to its aggressive character and relative resistance typical therapeutic approaches. Because biopsy not indicated in retinoblastoma, specific MRI features might be valuable identify children with this genetic subtype. Purpose To define the phenotype MYCNARB1+/+ evaluate ability qualitative help Materials Methods In retrospective, multicenter, case-control study, scans...
Bi-allelic germline mutations in the MUTYH gene give rise to multiple adenomas and an increased incidence of colorectal cancer. In addition, duodenal other extra-colonic manifestations have been described MUTYH-associated polyposis (MAP) patients. We describe two patients with bi-allelic carcinoma. The tumour Patient A was detected during evaluation non-specific abdominal complaints. B already diagnosed tens a colon carcinoma, when neoplasm detected. identification somatic G>T codon 12...
Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC in the immediate years following an FTP. No large prospective studies, however, have examined whether number and timing of pregnancies for
Both hereditary and nonhereditary retinoblastoma (Rb) are commonly initiated by loss of both copies the tumor suppressor gene ( RB1 ), while additional genomic changes required for initiation progression. Our aim was to determine whether there is heterogeneity between different clinical Rb subtypes. Therefore, 21 tumors from 11 patients 10 were analyzed using high‐resolution single nucleotide polymorphism (SNP) arrays losses gains validated with Multiplex Ligation‐dependent Probe...
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by seizures, mental retardation and the development of hamartomas in a variety organs tissues. The disease caused mutations either TSC1 gene on chromosome 9q34, or TSC2 16p13.3. products, TSC2, interact to form protein that inhibits signal transduction downstream effectors mammalian target rapamycin (mTOR). We have used combination different assays characterise effects number pathogenic amino acid substitutions...
An online decision aid to support persons having a genetic predisposition cancer and their partners during reproductive decision-making was developed. A two-phase usability test conducted among 12 couples (N = 22; 2 participated without partner) at risk for hereditary 15 health care providers. Couples providers expressed similar suggestions improvements, evaluated the modified as acceptable, easy use, comprehensible. The final pilot tested 16) with paired sample t tests comparing main...
Abstract Background Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary (PBC), especially in young patients with germline (g)BRCA–associated BC who already have high contralateral (CBC) risk and potentially increased genetic susceptibility to radiation. We sought investigate whether adjuvant RT PBC increases the of CBC gBRCA1/2-associated BC. Methods The gBRCA1/2 pathogenic variant carriers diagnosed were selected from prospective...
Introduction Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half the known TPSs are recognised during standard paediatric care. In current medical practice impossible to refer every patient geneticist, due limited capacity for routine consultation. Therefore, we have developed screening instrument identify high...
Abstract A nationwide pretest–posttest study was conducted in all clinical genetic centres the Netherlands, to evaluate effects of an online decision aid support persons who have a predisposition cancer and their partners making informed regarding reproductive options. Main outcomes (decisional conflict, knowledge, realistic expectations, level deliberation, self‐efficacy) were measured before use (T0), immediately after (T1), at 2 weeks (T2) aid. Paired sample t tests used compute...
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...
Individuals with Lynch syndrome have a pathogenic germline variant in one of the mismatch repair (MMR) genes (MLH1, MSH2/EPCAM, MSH6, or PMS2) and are often recognized based on MMR-deficient (dMMR) colorectal cancers (CRCs) endometrial (ECs).1Lynch H.T. et al.Clin Genet. 2009; 76: 1-18Crossref PubMed Scopus (555) Google Scholar,2Kunitomi H. al.Oncol Lett. 2017; 14: 3297-3301Crossref (17) Scholar Approximately 15% CRCs 20%–30% ECs dMMR, mostly due to MLH1-promoter hypermethylation. dMMR...