A5059544131- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Telomeres, Telomerase, and Senescence
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Ubiquitin and proteasome pathways
- Genomic variations and chromosomal abnormalities
- Cancer-related Molecular Pathways
University of Oulu
2018-2025
NordLab
2018-2023
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...
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 is strongly influenced by hereditary risk factors. Yet, the known susceptibility genes and genomic loci explain only about half of familial component disease. To identify novel breast predisposing gene defects, here we have performed massive parallel sequencing for Northern Finnish cases.Ninety-eight cases with indication disease were exome sequenced. Data filtering strategy focused on predictably deleterious rare variants that still enriched in sequenced cohort. Findings...
Strong inherited predisposition to breast cancer is estimated cause about 5-10% of all cases. As the known susceptibility genes, such as BRCA1 and BRCA2, explain only a fraction this, additional predisposing genes related biological mechanisms are actively being searched for. We have recently identified recurrent MCPH1 germline mutation, p.Arg304ValfsTer3, allele. encodes multifunctional protein involved in maintenance genomic integrity it also somatically altered various types, including...
Abstract CHEK2 is a well-established breast cancer susceptibility gene. The most frequent pathogenic variant 1100delC, loss-of-function mutation conferring 2-fold risk for cancer. This gene also harbors other rare variants encountered in the clinical panels hereditary One of these c.1312 G > T, p.(Asp438Tyr) kinase domain protein, but due to its rarity significance predisposition has remained unclear. Here, we tested prevalence allele showing enrichment Northern Finnish population, total...
Background: Rare variants of SORL1 have been associated with an increased risk early-onset or late-onset Alzheimer’s disease (AD). However, a lot remains to be clarified about their significance in the pathogenesis disease. Objective: To evaluate role among Finnish patients AD (EOAD). Methods: The rare SORL1variants were screened cohort 115 EOAD (mean age at onset 58.3 years, range 46–65 years) by using whole-exome sequencing. Results: We found one novel nonsense variant (p.Gln290*) and...
ABSTRACT Background Rare protein truncating variants of NTHL1 gene are causative for the recently described, recessively inherited tumor syndrome that is characterized by an increased lifetime risk colorectal cancer, polyposis, and breast cancer. Although there strong evidence cancer being a part spectrum in these families, role pathogenic susceptibility general population remains unclear. Methods We tested prevalence nonsense variant c.268C>T, p.Q90*, which major allele families also...
Abstract TINF2 is a critical subunit of the shelterin complex, which protects and maintains length telomeres. Pathogenic missense truncating mutations are causative for dyskeratosis congenita (DC), rare, dominantly inherited bone marrow failure syndrome characterized by mucocutaneous abnormalities cancer predisposition. Recent reports indicate that specific act as high penetrance predisposition alleles outside DC context, including breast in their tumor spectrum. Here, we have evaluated role...
Copy number variants (CNVs) are a major source of genetic variation and can disrupt genes or affect gene dosage. They known to be causal underlie predisposition various diseases. However, the role CNVs in inherited breast cancer susceptibility has not been thoroughly investigated. To address this, we performed whole-exome sequencing based analysis rare 98 high-risk Northern Finnish cases. After filtering, selected candidate alleles were validated characterized with combination orthogonal...