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Article
Open AccessVitamin C boosts DNA demethylation in TET2 germline mutation carriers
Accurate regulation of DNA methylation is necessary for normal cells to differentiate, develop and function. TET2 catalyzes stepwise DNA demethylation in hematopoietic cells. Mutations in the TET2 gene predispose...
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Article
Open AccessSequence determinants of human gene regulatory elements
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 the transcriptional activity of DNA sequences that rep...
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Article
Open AccessParity associates with chromosomal damage in uterine leiomyomas
Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are com...
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Article
Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma
One in four women suffers from uterine leiomyomas (ULs)—benign tumours of the uterine wall, also known as uterine fibroids—at some point in premenopausal life. ULs can cause excessive bleeding, pain and infert...
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Article
Open AccessRetrotransposon insertions can initiate colorectal cancer and are associated with poor survival
Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are u...
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Article
Open AccessAssociation analyses identify 31 new risk loci for colorectal cancer susceptibility
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ...
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Article
Open AccessImpact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemoki...
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Article
Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma
Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma with a poor prognosis: the 5-year survival rate is approximately 30%. Somatic driver mutations have been found in TET2, IDH2, D...
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Article
Discovery of potential causative mutations in human coding and noncoding genome with the interactive software BasePlayer
Next-generation sequencing (NGS) is routinely applied in life sciences and clinical practice, but interpretation of the massive quantities of genomic data produced has become a critical challenge. The genome-w...
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Article
The interaction landscape between transcription factors and the nucleosome
Nucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleos...
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Article
Open AccessContribution of allelic imbalance to colorectal cancer
Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalanc...
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Article
Open AccessGlobal metabolomic profiling of uterine leiomyomas
Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metab...
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Article
Open AccessMendelian randomisation analysis strongly implicates adiposity with risk of develo** colorectal cancer
Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a...
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Article
CTCF/cohesin-binding sites are frequently mutated in cancer
Lauri Aaltonen, Jussi Taipale and colleagues report frequent mutation of CTCF- and cohesin-binding sites (CBSs) in multiple cancer types. They find that the frequency of CBS mutations in microsatellite-stable ...
