Julika Borde
A5047726384- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Genomic variations and chromosomal abnormalities
- Ovarian cancer diagnosis and treatment
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Genetic and Kidney Cyst Diseases
- PARP inhibition in cancer therapy
- Coenzyme Q10 studies and effects
- Chronic Myeloid Leukemia Treatments
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Renal and related cancers
- Nutrition, Genetics, and Disease
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Intestinal and Peritoneal Adhesions
- Intestinal Malrotation and Obstruction Disorders
- Male Breast Health Studies
University Hospital Cologne
2018-2022
University of Cologne
2019-2022
Centrum für Integrierte Onkologie
2018-2021
German Sport University Cologne
2014
Abstract The prevalence of germ line mutations in non‐ BRCA 1/2 genes associated with hereditary breast cancer ( BC ) is low, and the role some these predisposition pathogenesis conflicting. In this study, 5589 consecutive index patients negative for pathogenic 2189 female controls were screened eight ATM , CDH 1 CHEK 2 NBN PALB RAD 51C 51D, TP 53 ). All met inclusion criteria German Consortium Hereditary Breast Ovarian Cancer testing. highest mutation was observed gene (2.5%), followed by...
Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while role of breast (BC) pathogenesis remains controversial. To assess deleterious germline BC/OC predisposition, 6341 well-characterized index patients with BC, 706 OC, and 2189 geographically matched female controls were screened loss-of-function (LoF) potentially damaging missense variants. All met inclusion criteria German Consortium Hereditary Breast Ovarian Cancer testing...
Abstract Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood spleen. Using expression quantitative trait loci (eQTL) reported these identify 26 previously unreported, likely target genes of overall risk variants, 17 for estrogen receptor (ER)-negative cancer, several with a known function. We...
Satellite cells (SCs) are the resident stem of skeletal muscle tissue which play a major role in adaptation, e.g. as response to physical training. The aim this study was examine effects an intermittent lactate (La) treatment on proliferation and differentiation C2C12 myoblasts, simulating microcycle high intensity endurance Furthermore, involvement reactive oxygen species (ROS) context examined. myoblasts were therefore repeatedly incubated for 2 h each day with 10 mM or 20 La medium (DM)...
The role of the BARD1 gene in breast cancer (BC) and ovarian (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess deleterious germline variants BC/OC a sample 4920 BRCA1/2-negative female index patients German Consortium for Hereditary Breast Ovarian Cancer (GC-HBOC). A total 4469 with BC, 451 OC, 2767 geographically matched control individuals were screened loss-of-function (LoF) mutations potentially damaging...
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs BRCA1/2 were overall cancer high grade (Gleason 8+) using an international sample 65 171 male PSV carriers cancer, 3,388 2,880 without the 3′ region (c.7914+) significantly elevated compared reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P 0.001], as well Gleason 8+ (HR 3.11; CI, 1.63–5.95;...
Background For individuals with ovarian cancer (OC), therapy options mainly depend on BRCA1/2 germline status. What is the prevalence of deleterious somatic variants, that is, does genetic tumour testing identify subgroups who also might benefit from targeted therapy? Methods Paired analysis tumour-derived versus blood-derived DNA to determine variants in OC predisposition genes ( ATM , BRCA1/2, BRIP1 MSH2/6 PALB2 RAD51C/D and TP53 ) PIK3CA PTEN (AGO-TR1 study, NCT02222883 ). Results were...
Abstract Background Genome-wide association studies suggest that the combined effects of breast cancer (BC)-associated single nucleotide polymorphisms (SNPs) can improve BC risk stratification using polygenic scores (PRSs). The performance PRSs in genome-wide studies–independent clinical cohorts is poorly studied individuals carrying mutations moderately penetrant predisposition genes such as CHEK2. Methods A total 760 female CHEK2 mutation carriers were included; 561 women affected with BC,...
Cancer patients are at risk of secondary therapy-related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)-associated genes t-MN factors, and their occurrence associated with cancer therapy age. Patients ovarian (OC) showed a particularly high prevalence CH-associated gene mutations, which may additionally be explained by the proportion hereditary disease cause this entity.We performed retrospective analysis 448 OC enrolled AGO-TR1 study; 249 were...
Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the BRCA2 gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated PVs BRCA1/2 and 23 non-BRCA1/2 using sample 614 patients mBC, recruited through centers German Consortium for Hereditary Breast Ovarian Cancer. A proportion mBC carried (23.0%, 142/614) BRCA1 (4.6%, 28/614). The was 11.0% without family history and/or ovarian...
Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.
The Li-Fraumeni cancer predisposition syndrome (LFS1) presents with a variety of tumor types and the TP53 gene is covered by most diagnostic panels. We demonstrate that deleterious variants identified in blood-derived DNA 523 patients ovarian (AGO-TR1 trial) were not causal for patients' three out six TP53-positive cases. In patients, mutations low variant fractions but patient seeking advice. analysis PPM1D genes, both intimately involved chemotherapy-induced and/or age-related clonal...
Abstract The contribution of germline copy number variants (CNVs) to risk developing cancer in individuals with pathogenic BRCA1 or BRCA2 remains relatively unknown. We conducted the largest genome-wide analysis CNVs 15,342 and 10,740 variant carriers. used these results prioritise a candidate breast risk-modifier gene for laboratory biological validation. Notably, HR deletions suggested an elevated estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI 1.09–1.35) compared...
The identification of germline copy number variants (CNVs) by targeted next-generation sequencing (NGS) frequently relies on in silico CNV prediction tools with unknown sensitivities. We investigated the performances four tools, including one commercial (Sophia Genetics DDM) and three non-commercial (ExomeDepth, GATK gCNV, panelcn.MOPS) 17 cancer predisposition genes 4208 female index patients familial breast and/or ovarian (BC/OC). predictions were verified via multiplex ligation-dependent...
Abstract Background Clinical management of women carrying a germline pathogenic variant (PV) in the BRCA1/2 genes demands for accurate age-dependent estimators breast cancer (BC) risks, which were found to be affected by variety intrinsic and extrinsic factors. Here we assess contribution polygenic risk scores (PRSs) occurrence extreme phenotypes with respect age at onset, namely, primary BC diagnosis before 35 years (early diagnosis, ED) cancer-free survival until 60 (late/no LD) female PV...
Variant-specific loss of heterozygosity (LOH) analyses may be useful to classify BRCA1/2 germline variants unknown significance (VUS). The sensitivity and specificity this approach, however, remains unknown. We performed comparative next-generation sequencing the genes using blood-derived tumour-derived DNA 488 patients with ovarian cancer enrolled in observational AGO-TR1 trial ( NCT02222883 ). Overall, 94 pathogenic, 90 benign 24 VUS were identified germline. A significantly increased...
Recent studies revealed a weak association of BARD1 germline loss-of-function (LoF) variants with breast cancer (BC). We determined the mutation prevalence in n = 3,348 well-characterized BC index patients German descent and geographically-matched female control individuals (GMCs; 2,196).
The role of BARD1 in breast cancer (BC) and ovarian (OC) predisposition remains elusive, as published case-control investigations have revealed controversial results. We aimed to assess the deleterious germline variants BC/OC predisposition. A total 4,469 BRCA1/2-negative female index patients with BC, 451 OC, 2,767 geographically-matched controls were screened for loss-of-function (LoF) mutations potentially damaging rare missense BARD1. All met inclusion criteria German Consortium...
Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic cause of failure. Because heterogeneity in progression ADPKD, parameters predicting future outcome are important. The disease-causing variant one these parameters.
Als Ursache einer familiären Häufung von Brust- und/oder Eierstockkrebs liegt in etwa 24 % der betroffenen Familien eine Keimbahnmutation den Hochrisikogenen BRCA1/2 vor [1]. In 6 BRCA1/2-negativen werden Keimbahnmutationen weiteren Risikogenen wie z. B. ATM, CHEK2, PALB2, RAD51C, RAD51 D oder TP53 nachgewiesen [2]. Allerdings variiert diesen die Erkrankungspenetranz, d. h., dass Erkrankungswahrscheinlichkeit trotz gleicher zugrunde liegender genetischer Veränderung schwankt. Es stellt sich...
Objective To identify acquired blood-specific mutations in clonal hematopoiesis (CH) genes that influence the risk of secondary, therapy-associated myeloid neoplasia.