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Uterine leiomyomas, or fibroids, are extremely common tumors. Regardless of their benign nature, fibroids can cause considerable morbidity. Women with African ancestry have a threefold increased risk of developing uterine leiomyomas with a greater symptom severity when compared to white women. Recently, we demonstrated that exon 2 of the MED12 gene is(More)
Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity. CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance. Understanding a mechanistic basis for CIN is therefore paramount. Here we find evidence for impaired(More)
Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by(More)
Classical models of tumorigenesis assume that the mutations which cause tumours to grow act in a cell-autonomous fashion. This is not necessarily true. Sometimes tumour cells may adopt genetic strategies that boost their own replication and which also influence other cells in the tumour, whether directly or as a side-effect. Tumour growth as a whole might(More)
To identify risk variants for childhood acute lymphoblastic leukemia (ALL), we conducted a genome-wide association study of two case-control series, analyzing the genotypes with respect to 291,423 tagging SNPs in a total of 907 ALL cases and 2,398 controls. We identified risk loci for ALL at 7p12.2 (IKZF1, rs4132601, odds ratio (OR) = 1.69, P = 1.20 x(More)
To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies(More)
Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known(More)
BACKGROUND Fumarate hydratase (HGNC approved gene symbol - FH), also known as fumarase, is an enzyme of the tricarboxylic acid (TCA) cycle, involved in fundamental cellular energy production. First described by Zinn et al in 1986, deficiency of FH results in early onset, severe encephalopathy. In 2002, the Multiple Leiomyoma Consortium identified(More)
Accurate duplication of DNA prior to cell division is essential to suppress mutagenesis and tumour development. The high fidelity of eukaryotic DNA replication is due to a combination of accurate incorporation of nucleotides into the nascent DNA strand by DNA polymerases, the recognition and removal of mispaired nucleotides (proofreading) by the exonuclease(More)
Next-generation sequencing (NGS) of cancer genomes promises to revolutionise oncology, with the ability to design and use targeted drugs, to predict outcome and response, and to classify tumours. It is continually becoming cheaper, faster and more reliable, with the capability to identify rare yet clinically important somatic mutations. Technical challenges(More)