Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer ( TOC ) minimal region on 17q25 to 42.5�kb: sequencing does not identify the causative gene

Langan, Joanne E.; Cole, Charlotte G.; Huckle, Elisabeth J.; Byrne, Shaun; McRonald, Fiona E.; Rowbottom, Lynn; Ellis, Anthony; Shaw, J.M.; Leigh, Irene M.; Kelsell, David P.; Dunham, Ian; Field, John K.; Risk, Janet M.

doi:10.1007/s00439-004-1100-3

Cited by 34 publications

(5 citation statements)

References 17 publications

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“…Currently, a rare autosomal dominant disorder defined by a genetic abnormality on chromosome 17q25 is the only recognised familial syndrome that predisposes patients to squamous cell carcinoma of the oesophagus [36]. The present study has provided some modeling parameters of oesophageal cancer for further genetic linkage studies.…”

Section: Discussionmentioning

confidence: 89%

Genetic Heterogeneity of Oesophageal Cancer in High-Incidence Areas of Southern and Northern China

et al. 2010

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Background and ObjectiveOesophageal cancer is one of the most common and deadliest cancers worldwide. Our previous population-based study reported a high prevalence of oesophageal cancer in Chaoshan, Guangdong Province, China. Ancestors of the Chaoshan population migrated from the Taihang Mountain region of north-central China, which is another high-incidence area for oesophageal cancer. The purpose of the present study was to obtain evidence of inherited susceptibility to oesophageal cancer in the Chaoshan population, with reference to the Taihang Mountain population, with the eventual goal of molecular identification of the disease genes.MethodsWe conducted familial correlation, commingling, and complex segregation analyses of 224 families from the Chaoshan population and 403 families from the Taihang population using the FPMM program of S.A.G.E. version 5.3.0. A second analysis focused on specific families having large numbers of affected individuals or early onset of the disease.ResultsFor the general population, moderate sib-sib correlation was noticed for esophageal cancer. Additionally, brother-brother correlation was even higher. Commingling analyses indicated that a three-component distribution model best accounts for the variation in age of onset of oesophageal cancer, and that a multifactorial model provides the best fit to the general population data. An autosomal dominant mode and a dominant or recessive major gene with polygenic inheritance were found to be the best models of inherited susceptibility to oesophageal cancer in some large families.ConclusionsThe current results provide evidence for inherited susceptibility to oesophageal cancer in certain high-risk groups in China, and support efforts to identify the susceptibility genes.

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Section: Discussionmentioning

confidence: 89%

Genetic Heterogeneity of Oesophageal Cancer in High-Incidence Areas of Southern and Northern China

et al. 2010

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“…Although CYGB is not mutated in tylotic individuals [31] or in a series of sporadic squamous cell oesophageal carcinomas [34], we have shown that its expression is strongly downregulated in non-cancerous oesophageal biopsies from patients with TOC compared with normal biopsies [33]. CYGB is also methylated and downregulated in sporadic oesophageal, lung and head and neck cancers [27], [28], [33].…”

Section: Introductionmentioning

confidence: 75%

Protection from Intracellular Oxidative Stress by Cytoglobin in Normal and Cancerous Oesophageal Cells

2012

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Cytoglobin is an intracellular globin of unknown function that is expressed mostly in cells of a myofibroblast lineage. Possible functions of cytoglobin include buffering of intracellular oxygen and detoxification of reactive oxygen species. Previous work in our laboratory has demonstrated that cytoglobin affords protection from oxidant-induced DNA damage when over expressed in vitro, but the importance of this in more physiologically relevant models of disease is unknown. Cytoglobin is a candidate for the tylosis with oesophageal cancer gene, and its expression is strongly down-regulated in non-cancerous oesophageal biopsies from patients with TOC compared with normal biopsies. Therefore, oesophageal cells provide an ideal experimental model to test our hypothesis that downregulation of cytoglobin expression sensitises cells to the damaging effects of reactive oxygen species, particularly oxidative DNA damage, and that this could potentially contribute to the TOC phenotype. In the current study, we tested this hypothesis by manipulating cytoglobin expression in both normal and oesophageal cancer cell lines, which have normal physiological and no expression of cytoglobin respectively. Our results show that, in agreement with previous findings, over expression of cytoglobin in cancer cell lines afforded protection from chemically-induced oxidative stress but this was only observed at non-physiological concentrations of cytoglobin. In addition, down regulation of cytoglobin in normal oesophageal cells had no effect on their sensitivity to oxidative stress as assessed by a number of end points. We therefore conclude that normal physiological concentrations of cytoglobin do not offer cytoprotection from reactive oxygen species, at least in the current experimental model.

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“…35 Another example is CYGB expression, the fifth most important feature. CYGB shows variable expression in cancers: it is down-regulated in many cancers 36 but up-regulated in lung and brain metastases, and head and neck cancer. 37,38 The methylation level at a LAMA4 promoter CpG was found as the seventh most important feature; previously, the aberrant methylation at the LAMA4 promoter was observed in breast carcinoma 39 and low methylation was associated with poor progression-free survival.…”

Section: Resultsmentioning

confidence: 99%

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

Fan

Tang

et al. 2019

npj Genomic Med

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The integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450 K BeadChip (Illumina 450 K array) that only covers about 1.5% of CpGs in the human genome. Therefore, increasing the coverage of the DNA methylome would significantly leverage the usage of the TCGA data. Here, we present a new model called EAGLING that can expand the Illumina 450 K array data 18 times to cover about 30% of the CpGs in the human genome. We applied it to analyze 13 cancers in TCGA. By integrating the expanded methylation, gene expression, and somatic mutation data, we identified the genes showing differential patterns in each of the 13 cancers. Many of the triple-evidenced genes identified in majority of the cancers are biomarkers or potential biomarkers. Pan-cancer analysis also revealed the pathways in which the triple-evidenced genes are enriched, which include well known ones as well as new ones, such as axonal guidance signaling pathway and pathways related to inflammatory processing or inflammation response. Triple-evidenced genes, particularly TNXB, RRM2, CELSR3, SLC16A3, FANCI, MMP9, MMP11, SIK1, and TRIM59 showed superior predictive power in both tumor diagnosis and prognosis. These results have demonstrated that the integrative analysis using the expanded methylation data is powerful in identifying critical genes/pathways that may serve as new therapeutic targets.

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Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer ( TOC ) minimal region on 17q25 to 42.5�kb: sequencing does not identify the causative gene

Cited by 34 publications

References 17 publications

Genetic Heterogeneity of Oesophageal Cancer in High-Incidence Areas of Southern and Northern China

Genetic Heterogeneity of Oesophageal Cancer in High-Incidence Areas of Southern and Northern China

Protection from Intracellular Oxidative Stress by Cytoglobin in Normal and Cancerous Oesophageal Cells

Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers

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