A5079139506- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Bladder and Urothelial Cancer Treatments
- Uterine Myomas and Treatments
- Colorectal Cancer Treatments and Studies
- Urinary and Genital Oncology Studies
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Endometriosis Research and Treatment
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Gynecological conditions and treatments
- Colorectal Cancer Screening and Detection
- Genomics and Rare Diseases
- Genetic Associations and Epidemiology
- Cancer, Lipids, and Metabolism
- Lymphoma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Congenital Heart Disease Studies
- Congenital heart defects research
- Cancer-related gene regulation
University of Helsinki
2015-2025
Helsinki University Hospital
1988-2024
Blueprint Genetics (Finland)
2024
Genomics (United Kingdom)
2021
Karolinska Institutet
2016-2021
Reaction Biology (Germany)
2014-2016
Medical Genetics Center
2013
Hyvinkää Hospital
1993-2012
Centre for Human Genetics
2010
Institute of Cancer Research
2010
Positives and negatives of methylated CpG When the DNA bases cytosine guanine are next to each other, a methyl group is generally added pyrimidine, generating mCpG dinucleotide. This modification alters structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. systematically analyzed effect methylation on binding 542 human TFs (see Perspective Hughes Lambert). In addition some TFs, they found that mCpGs promote others, particularly involved in...
Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and can cause considerable morbidity. To study the genetic basis this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing identified tumor-specific mutations in mediator complex subunit 12 (MED12) gene 10. Through analysis 207 additional tumors, determined MED12 is altered 70% (159 225) a total 80 patients. The Mediator 26-subunit transcriptional...
Uterine leiomyomas are benign but affect the health of millions women. A better understanding molecular mechanisms involved may provide clues to prevention and treatment these lesions.We performed whole-genome sequencing gene-expression profiling 38 uterine corresponding myometrium from 30 women.Identical variants observed in some separate tumor nodules suggested that have a common origin. Complex chromosomal rearrangements resembling chromothripsis were feature leiomyomas. These best...
Abstract Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has strong heritable basis. We report genome-wide association analysis 34,627 CRC cases 71,379 controls European ancestry that identifies SNPs at 31 new risk loci. also identify eight independent the previously reported loci, further nine loci only identified in Asian populations. use situ promoter capture Hi-C (CHi-C), gene expression, silico annotation methods to likely target genes SNPs. Whilst...
Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women's health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation...
Abstract DNA can determine where and when genes are expressed, but the full set of sequence determinants that control gene expression is unknown. Here, we measured transcriptional activity sequences represent an ~100 times larger space than human genome using massively parallel reporter assays (MPRAs). Machine learning models revealed transcription factors (TFs) generally act in additive manner with weak grammar most enhancers increase from a promoter by mechanism does not appear to involve...
ARID1A has been identified as a novel tumor suppressor gene in ovarian cancer and subsequently various other types. belongs to the ARID domain containing family, which comprises of 15 genes involved, for example, transcriptional regulation, proliferation chromatin remodeling. In this study, we used exome sequencing data analyze mutation frequency all 25 microsatellite unstable (MSI) colorectal cancers (CRCs) first systematic effort characterize pattern whole family. Genes fulfilled selection...
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) levels total (TC), triglyceride (TG), low‐density lipoprotein (LDL), high‐density (HDL) as instrumental variables (IV). calculated MR estimates for each factor...
Abstract Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly cardiovascular disease increased cytokine chemokine expression as reported in mice. Here, we discover a germline mutation lymphoma family. We observe neither unusual predisposition atherosclerosis nor abnormal pro-inflammatory or expression. The latter finding confirmed cells from three additional unrelated carriers. defect elevates...
The somatic landscape of pituitary adenomas is largely unknown. Identification alterations aims at better understanding tumor pathology. objective the study was a genome-wide characterization single-nucleotide variants, structural and copy-number aberrations in somatotropinomas. Whole-genome sequencing polymorphism array analyses were performed on 12 fresh-frozen somatotropinomas their corresponding blood samples. All coding variants confirmed by Sanger sequencing. Studied tumors Apart from...
Uterine leiomyomas (ULs) are benign tumors that a major burden to women's health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects alleles were evaluated view molecular clinical characteristics. 22 loci displayed significant association. The likely predisposition genes could be grouped two biological processes. Genes involved genome stability represented TERT, TERC, OBFC1 - highlighting...
Abstract Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active several human cancers, particular those gastrointestinal tract. Here we characterize retrotransposon insertions 202 tumor whole genomes and investigate their associations with molecular clinical characteristics. We find highly variable activity among...
The gene desert upstream of the MYC oncogene on chromosome 8q24 contains susceptibility loci for several major forms human cancer. region shows high conservation between and mouse multiple enhancers that are activated in tumor cells. However, role this normal development has not been addressed. Here we show a 538 kb deletion entire super-enhancer mice results 50% to 80% decrease Myc expression tissues. viable no overt phenotype. they resistant tumorigenesis, most cells isolated from them...
// Esa Pitkänen 1,2 , Tatiana Cajuso Riku Katainen Eevi Kaasinen Niko Välimäki Kimmo Palin Jussi Taipale 1,3 Lauri A. Aaltonen and Outi Kilpivaara 1 Genome-Scale Biology Research Program, Programs Unit, University of Helsinki, Finland 2 Department Medical Genetics, 3 Science for Life Center, Biosciences Nutrition, Karolinska Institutet, Stockholm, Sweden Correspondence: Aaltonen, email: Keywords : colorectal cancer, genome, sequencing, retrotransposon, L1 Received February 10, 2014 Accepted...