Isabel Spier
A5045240720- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Colorectal Cancer Treatments and Studies
- Genomic variations and chromosomal abnormalities
- Gastric Cancer Management and Outcomes
- BRCA gene mutations in cancer
- Digestive system and related health
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Colorectal Cancer Screening and Detection
- Metastasis and carcinoma case studies
- Gastrointestinal Tumor Research and Treatment
- Cancer-related gene regulation
- Helicobacter pylori-related gastroenterology studies
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- Virus-based gene therapy research
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Hedgehog Signaling Pathway Studies
- Glioma Diagnosis and Treatment
- Genetic Syndromes and Imprinting
National Center for Tumor Diseases
2020-2025
University Hospital Bonn
2013-2025
University of Bonn
2015-2025
Research Network (United States)
2023-2024
ERN GUARD-Heart
2022-2023
ERN GENTURIS
2023
The Ohio State University
2023
University of Wisconsin–Madison
2022
Praxis für Humangenetik
2012-2019
German Cancer Research Center
2007-2012
In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome/HNPCC, no germline alteration in the APC, MUTYH, mismatch repair (MMR) genes are found. Missense mutations polymerase POLE and POLD1 have recently been identified as rare cause multiple adenomas carcinomas, condition termed proofreading-associated (PPAP). The aim present study was to evaluate clinical relevance phenotypic spectrum mutations. Therefore, targeted sequencing POLD1, POLD2, POLD3, POLD4,...
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 Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, 3-year prospective study, we evaluated novel diagnostic concept based on multidisciplinary expertise in Germany. Here present the systematic investigation of phenotypic and molecular genetic data 1,577 patients who had undergone exome sequencing were partially analyzed next-generation phenotyping approaches....
PurposeJuvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants SMAD4 and BMPR1A. We aimed to gather detailed clinical molecular genetic information on JPS disease expression provide basis for management guidelines establish open access variant databases.MethodsWe performed retrospective, questionnaire-based European multicenter survey established cohort SMAD4/BMPR1A carriers from...
The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Tumours and Clinical Genome Resource, who set out to develop recommendations interpretation of germline APC variants underlying Familial Adenomatous Polyposis, most frequent hereditary polyposis syndrome.
Abstract Background and aims Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for stratification. Methods To assess combined impact PRS other main factors on CRC risk, 163,516 individuals from UK Biobank were stratified as follows: 1. carriers status germline pathogenic (PV) susceptibility genes ( APC, MLH1, MSH2, MSH6, PMS2) , 2. (< 20%), intermediate (20–80%), or high (> 80%), 3....
To uncover pathogenic deep intronic variants in patients with colorectal adenomatous polyposis, whom no germline mutation the APC or MUTYH genes can be identified by routine diagnostics, we performed a systematic messenger RNA analysis 125 unrelated mutation-negative cases. Overall, aberrant transcripts 8% of (familial cases 30%; early-onset manifestation 21%). In eight them, two different out-of-frame pseudoexons were found consisting 167-bp insertion from intron 4 five families shared...
To uncover novel causative genes in patients with unexplained adenomatous polyposis, a model disease for colorectal cancer, we performed genome-wide analysis of germline copy number variants (CNV) large, well characterized APC and MUTYH mutation negative patient cohort followed by targeted next generation sequencing (NGS) approach. Genomic DNA from 221 unrelated German was genotyped on high-resolution SNP arrays. Putative CNVs were filtered according to stringent criteria, compared those 531...
<h3>Background</h3> In 30–50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes <i>APC,</i> causing familial <i>MUTYH,</i> <i>MUTYH</i>-associated or <i>POLE</i> <i>POLD1</i>, polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore impact <i>APC</i> mutational mosaicism unexplained polyposis. <h3>Methods</h3> To comprehensively screen for somatic low-level mosaicism,...
This study sought to characterize the ophthalmic and extraocular phenotype in patients with known novel KIF11 mutations.Four (3, 5, 36, 38 years of age, on father-daughter constellation) from three unrelated families were characterized by retinal examination including multimodal imaging, investigation for syndromic disease manifestations, targeted next-generation sequencing. The subcellular localization Kif11 retina was analyzed light electron microcopy.There considerable interindividual...
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...
Background & AimsConstitutional mismatch repair deficiency (CMMRD) is a rare recessive childhood cancer predisposition syndrome caused by germline variants. Constitutional microsatellite instability (cMSI) CMMRD diagnostic hallmark and may associate with risk. We quantified cMSI in large patient cohort to explore genotype–phenotype correlations using novel MSI markers selected for blood.MethodsThree CMMRD, 1 Lynch syndrome, 2 control blood samples were genome sequenced >120× depth. A pilot...
Abstract Pediatric high-grade glioma (pedHGG) can occur as first manifestation of cancer predisposition syndromes resulting from pathogenic germline variants in the DNA mismatch repair (MMR) genes MSH2 , MSH6 MLH1 and PMS2 . The aim this study was to establish a generalized screening for Lynch syndrome constitutional MMR deficiency (CMMRD) pedHGG patients, detection deficiencies (MMRD) may enable upfront therapeutic use checkpoint inhibitors identification variant carriers patients’...
Abstract Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the tumor suppressor gene APC . Confirmation of diagnosis was not achieved cancer panel and exome sequencing or custom array-CGH a family with suspected FAP across five generations. Long-read genome (PacBio), short-read (Illumina), RNA sequencing, further validations were performed different tissues multiple members. resolved 6 kb full-length intronic insertion heterozygous LINE-1 element between exons...