A5086907778- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Genetic Associations and Epidemiology
- Genetic factors in colorectal cancer
- Immunodeficiency and Autoimmune Disorders
- Genomics and Chromatin Dynamics
- Prenatal Screening and Diagnostics
- Lymphoma Diagnosis and Treatment
- Lipid metabolism and biosynthesis
- Retinal Development and Disorders
- Sleep and related disorders
- Genomics and Rare Diseases
- Vestibular and auditory disorders
- Chromosomal and Genetic Variations
- Acute Myeloid Leukemia Research
- Hearing, Cochlea, Tinnitus, Genetics
- Chronic Lymphocytic Leukemia Research
- Bioinformatics and Genomic Networks
- Blood disorders and treatments
- Endoplasmic Reticulum Stress and Disease
- Machine Learning in Healthcare
- Genomics and Phylogenetic Studies
- Viral-associated cancers and disorders
University of Oulu
2016-2025
Northern Ostrobothnia Hospital District
2019-2025
Borealis (Finland)
2019-2025
Radboud University Nijmegen
2019-2024
Radboud University Medical Center
2019-2024
University of Helsinki
2020-2024
Helsinki University Hospital
2024
Radboud Institute for Molecular Life Sciences
2020-2023
NordLab
2014-2023
Institute for Molecular Medicine Finland
2020-2023
Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by acute respiratory syndrome 2 (SARS-CoV-2).To explore the presence of genetic variants associated with among young COVID-19.Case series pairs brothers history meeting selection criteria (age <35 years) brother admitted intensive care unit (ICU) due COVID-19. Four...
ABSTRACT Myelodysplastic neoplasia with complex karyotype (CK‐MDS) poses significant clinical challenges and is associated poor survival. Detection of structural variants (SVs) crucial for diagnosis, prognostication, treatment decision‐making in MDS. However, the current standard‐of‐care (SOC) cytogenetic testing, relying on karyotyping, often yields ambiguous results cases CK. Here, SV detection by novel optical genome mapping (OGM) technique was explored 15 CK‐MDS cases, which collectively...
Abstract Micropapillary colorectal adenocarcinoma is a morphologic subtype of cancer (CRC) with insufficiently characterized prognostic significance and biological features. We analyzed the histopathological, immunological, features micropapillary in two independent CRC cohorts ( N = 1,876). found that adenocarcinomas accounted for 4.9% 6.4% CRCs cohorts. A growth pattern was associated advanced stage lymphovascular invasion p < 0.001), but also shorter overall survival these factors...
Abstract Purpose Several variants in DNA damage response (DDR) genes increase the probability to develop breast cancer and show enrichment Northern Finland. Here, population prevalence risk estimations were refined for sixteen recurrent pathogenic/likely pathogenic DDR gene variants. Methods Variant genotyping was performed 2343 unselected Finnish cases 4607 cancer-free controls, tumor features family history of carriers examined. Results Based on their carrier history, studied BRCA1 BRCA2...
Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray (CMA). Optical genome mapping (OGM), a novel technique based on imaging long DNA molecules labeled at specific sites, allows identification multiple cytogenetic abnormalities single test. We aimed to determine whether OGM is suitable alternative cytogenomic assessment CLL,...
The fluorescence in situ hybridization (FISH) technique plays an important role the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible a diagnostic setup. Optical genome mapping (OGM) novel for high-resolution detection structural variants (SVs), previous studies have...
In a subset of pediatric cancers, germline cancer predisposition is highly suspected based on clinical and pathological findings, but genetic evidence lacking, which hampers counseling predictive testing in the families involved. We describe family with two siblings born from healthy parents who were both neonatally diagnosed atypical teratoid rhabdoid tumor (ATRT). This rare aggressive associated biallelic inactivation SMARCB1, 30% cases, predisposing mutation Whereas tumors showed loss...
The FANCM c.5101C>T nonsense mutation was previously found to associate with breast cancer in the Finnish population, especially among triple-negative cases. Here, we studied prevalence of three other variants: c.5791C>T, which has been reported predispose familial cancer, and c.4025_4026delCT c.5293dupA variants recently identified patients.We genotyped c.5791C>T 4806 invasive patients, including BRCA1/2 negative cases unselected cases, 2734 healthy population controls from four different...
Abstract Somatic structural variants are important for cancer development and progression. In a diagnostic set-up, especially hematological malignancies, the comprehensive analysis of all cytogenetic aberrations in given sample still requires combination techniques, such as karyotyping, fluorescence situ hybridization CNV-microarrays. We hypothesize that these classical approaches could be replaced by high-resolution genome imaging. Bone marrow aspirates or blood samples derived from 48...
Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed targeted next-generation sequencing 796 genes implicated in DNA repair 189 Finnish breast cases with indication disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3) was identified early damage response gene, MCPH1, significantly associating both familial (5/145, 3.4%, P =...
Diffuse large B-cell lymphoma (DLBCL) is an aggressive with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, concurrent immunohistochemical (IHC) high expression BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also worse outcome. Our aim was evaluate the aforementioned issues in a cohort 155 patients uniformly treated R-CHOP-like therapies. We performed direct sequencing TP53 exons 5, 6, 7 8 as well fluorescence in-situ...
Abstract Chromosomal aberrations and structural variations are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics, karyotyping CNV-microarrays, spite the low resolution first one inability to detect neither balanced SVs nor provide genomic localization or orientation duplicated segments, latter. We here investigated utility high optical mapping by genome imaging for patients carrying known chromosomal context constitutional...
Abstract Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel factors, 39 truncating mutations, identified 189 Northern Finnish hereditary patients parallel sequencing 796 DDR genes, were studied for disease association. Mutation screening was performed cases (n = 578–1565) controls 337–1228). Mutations...
The lack of molecular diagnoses in rare genetic diseases can be explained by limitations current standard genomic technologies. Upcoming long-read techniques have complementary strengths to overcome these limitations, with a particular strength identifying structural variants. By using optical genome mapping and sequencing, we aimed identify the pathogenic variant large family X-linked choroideremia. In this family, aberrant splicing exon 12 choroideremia gene CHM was detected 2003, but...
Background: Myocardial fibrosis is a common postmortem finding among young individuals with sudden cardiac death. Because there no known single cause, we tested the hypothesis that some cases of myocardial in absence identifiable causes (primary [PMF]) are associated genetic variants. Methods: Tissue was obtained at autopsy from 4031 consecutive death Northern Finland, whom PMF only structural 145 subjects We performed targeted next-generation sequencing using panel 174 genes structure and...
Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but contribution other FA genes has remained questionable. Due to FA's rarity, finding recurrent deleterious mutations among families is challenging. The use founder populations, such as Finns, could provide some advantage this. Here, we have resolved complementation groups causative five patients, representing first mutation confirmed cases...
Several known breast cancer susceptibility genes with moderate-to-high risk alleles encode proteins involved in DNA damage response (DDR). As these explain less than half of the hereditary cases, additional predisposing are likely to be discovered. Many previous studies utilizing massive parallel sequencing have focused on protein-truncating variants, and role rare missense mutations has remained poorly addressed. To identify novel factors, we systematically analyzed data from our 796 DDR...
Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics genetic variation may affect the clinical outcome. The FANCM c.5101C > T nonsense mutation in Finnish population associates with increased risk of breast cancer, especially for triple-negative patients. To investigate association disease prognosis, we studied phenotype, treatment outcome, patient survival 3,933 invasive patients, including 101 carriers 3,832 non-carriers. We also examined nuclear...