A5041770166- BRCA gene mutations in cancer
- Nutrition, Genetics, and Disease
- Genetic factors in colorectal cancer
- PI3K/AKT/mTOR signaling in cancer
- Ovarian cancer diagnosis and treatment
- Cancer Genomics and Diagnostics
- Global Cancer Incidence and Screening
- PARP inhibition in cancer therapy
- Colorectal Cancer Screening and Detection
- DNA Repair Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer Diagnosis and Treatment
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Infectious Diseases and Mycology
- Intellectual Property Rights and Media
- Prenatal Screening and Diagnostics
- Genetic Associations and Epidemiology
- Cancer and Skin Lesions
- Polyomavirus and related diseases
- Colorectal and Anal Carcinomas
- Endometrial and Cervical Cancer Treatments
- Breast Lesions and Carcinomas
- Mast cells and histamine
- Thyroid Cancer Diagnosis and Treatment
Radboud University Nijmegen
2018-2025
Radboud University Medical Center
2018-2025
University Medical Center
2019-2024
ERN GENTURIS
2022-2024
Innsbruck Medical University
2024
ERN GUARD-Heart
2022-2024
University Medical Center Hamburg-Eppendorf
2024
Universität Hamburg
2024
Università Cattolica del Sacro Cuore
2024
Leiden University Medical Center
2024
Genetic diagnosis of rare diseases requires accurate identification and interpretation genomic variants. Clinical molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree rare-disease data (94.5% exomes, 5.5% genomes), performed systematic reanalysis for 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed 6,004 families. We established a collaborative, two-level review...
PTEN hamartoma tumour syndrome is a diverse multi-system disorder predisposing to the development of hamartomatous growths, increasing risk breast, thyroid, renal cancer, and possibly endometrial colorectal cancer melanoma. There no international consensus on surveillance in PHTS all current guidelines are based expert opinion. A comprehensive literature review was undertaken were developed by clinicians with expertise from clinical genetics, gynaecology, endocrinology, dermatology,...
Abstract Background Women with epithelial ovarian cancer (OC) have a higher chance to benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) therapy if their tumor has somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise genetic predisposition testing for all OC patients, though this does not detect variants. We assessed the feasibility of workflow universal DNA newly diagnosed patients as prescreen PARPi treatment and testing. Methods Formalin-fixed...
PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with 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 are likely overestimated due to ascertainment bias. We aimed provide more accurate personalized risks.This was European, adult PHTS cohort study data from medical files, registries, and/or questionnaires. Cancer hazard ratios were assessed Kaplan-Meier Cox regression...
Purpose: Females with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals monoallelic gPVs.This study is aimed at expanding the knowledge on occurrence of other malignancies.Methods: Exome sequencing who developed primary malignancies identified three (NM_007194.4)c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a state.We collected phenotypes an additional cohort gPVs (n=291).Results: In total, 157 (53.4%; 157/294...
Increased hereditary cancer risk is one of the hallmarks PTEN Hamartoma Tumor Syndrome (PHTS) which caused by a pathogenic germline variant in PTEN. Case reports and some cohort studies have described ovarian (OC) PHTS patients. Previously, we observed an enrichment non-serous OC compared to sporadic cases (3% vs 1%). However, currently not considered PHTS-related cancer. The aim this study was describe five patients with OC. Three OCs were mucinous carcinomas (49, 51 52 years) two malignant...
Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic OC highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using tumor DNA test as prescreen testing, (ii) Germline-First referring all patients the clinical geneticist testing.Tumor-First were compared scenarios; real-world uptake setting implementation 100%. Decision analytic models...
Approximately 27–36 million patients in Europe have one of the ~ 5.000–8.000 known rare diseases. These often do not receive care they need or a substantial delay from diagnosis to treatment. In March 2017, twenty-four European Reference Networks (ERNs) were launched with aim improve for these through cross border healthcare, way that medical knowledge and expertise travels across borders, rather than patients. It is expected ERNs, disease get access expert more quickly, research guideline...
Universal mismatch repair deficiency (dMMR) testing of colorectal cancer (CRC) is promoted as routine diagnostics to prescreen for Lynch syndrome. We evaluated the yield and experience age-related molecular investigation heritable nonheritable causes dMMR in CRC below age 70 identify Syndrome. In a prospective cohort 3602 newly diagnosed CRCs from 19 hospitals, dMMR, MLH1 promoter hypermethylation, germline MMR gene somatic was assessed daily practice. Yield using data Dutch Pathology...
Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas microsatellite instability (MSI-H) mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy immune checkpoint inhibitors. Our aim is assess how often other tumor types in individuals share characteristics.We retrieved the full history a historical clinic-based cohort 1745 calculated standardized incidence ratio for all types. MSI status, somatic second hit...
Pathogenic PTEN germline variants cause Hamartoma Tumor Syndrome (PHTS), a rare disease with variable genotype and phenotype. Knowledge about these spectra genotype-phenotype associations could help diagnostics potentially lead to personalized care. Therefore, we assessed the PHTS phenotype spectrum in large cohort study.Information was collected of 510 index patients pathogenic or likely (LP/P) (n = 467) uncertain significance. Genotype-phenotype were using logistic regression analyses...
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 their increased cancer risk. We aimed to describe the spectrum, onset histopathological characteristics assess whether specific could improve PHTS recognition. Genetic testing results pathology reports were collected for tested germline variants between 1997 2020 from diagnostic laboratory Dutch nationwide...
Annual MRI and mammography is recommended for BRCA1/2 mutation carriers to reduce breast cancer mortality. Less intensive screening advised ≥60 years, although effectiveness unknown. We identified without bilateral mastectomy before age 60 determine whom relevant, in the Rotterdam Family Cancer Clinic HEBON: a nationwide prospective cohort study. Furthermore, we compared tumour stage at diagnosis between different strategies ≥60. Tumours >2 cm, positive lymph nodes, or distant metastases...
Patients with PTEN Hamartoma Tumour Syndrome (PHTS) are at increased risk of developing cancer. Many adult PHTS patients not recognized as such and do receive the cancer surveillance they need. Our aim was to define phenotypic characteristics that can easily be assessed manifest by early adulthood, hence could serve red flags (i.e. alerting signals) for recognition high PHTS. Phenotypic including macrocephaly, multinodular goitre (MNG), oral features were examined in 81 paediatric 86 one two...
We aimed to quantify previously observed relatively high cancer risks in BRCA2 mutation carriers (BRCA2 carriers) older than 60 the Northern Netherlands, and analyze whether these could be explained by spectrum or population background risk.This consecutive cohort study included all known pathogenic BRCA1/2 Netherlands (N = 1,050). Carrier general reference populations were: rest of 2,013) both regions. Regional differences were assessed with HRs ORs. adjusted for birth year spectrum.All...
Individuals with germline pathogenic variants in BRCA1 or BRCA2 are at a high risk of breast and ovarian carcinomas BRCA1/2 deficiency homologous recombination that can be detected by analysis genome-wide genomic instability features such as large-scale state transitions, telomeric allelic imbalances, loss heterozygosity. Malignancies more sensitive to platinum-based therapies poly(ADP-ribose) polymerase inhibitors. We investigated the fraction non-breast malignancies have features.
Women with PTEN Hamartoma Tumor Syndrome (PHTS) are offered breast cancer (BC) surveillance because of an increased BC lifetime risk. Surveillance guidelines are, however, expert opinion-based a lack data. We aimed to assess the yield and effectiveness prevalence type disease in women PHTS.Sixty-five PHTS who visited our center between 2001 2021 were included. consisted annual magnetic resonance imaging (MRI) mammography from ages 25 30 years, respectively.Thirty-nine enrolled program...
Paternal transmission of a BRCA mutation has been reported to increase the risk breast cancer in offspring more than when is maternally inherited. As this effect might be caused by referral bias, aim study was assess parent-of-origin BRCA1/2 on lifetime risk, adjusted for bias.A Dutch national cohort including 1,314 proven carriers and covering 54,752 person years. Data were collected family clinics, via questionnaires from Cancer Registry. The assessed using Cox regression analyses, both...