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  • 1
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    Online Resource
    Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel
    Oxford University Press (OUP) ; 2013
    In:  Human Molecular Genetics Vol. 22, No. 15 ( 2013-8-1), p. 3038-3047
    Details
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 22, No. 15 ( 2013-8-1), p. 3038-3047
    Type of Medium: Online Resource
    ISSN: 1460-2083 , 0964-6906
    URL: Article
    DOI: 10.1093/hmg/ddt160
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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  • 2
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    Abstract 3640: Age-related DNA methylation in normal breast tissues.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 3640-3640
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 3640-3640
    Abstract: Age-related DNA methylation in normal breast tissues It is well established that age is a key risk factor for breast cancer, with increasing incidence associated with older age. Epigenetic mechanisms, such as DNA methylation alterations, may contribute to age-related increases in breast cancer risk. Altered patterns of DNA methylation can modify the regulation of gene expression or expression potential, and DNA methylation alterations are frequently observed in the early stages of breast tumorigenesis. However, genome-wide interindividual variation in normal breast DNA methylation has not been well characterized for its relation with age and other key breast cancer risk factors. To investigate the relationship between age and DNA methylation in normal breast tissues, we first performed a meta-analysis using two independent data sets GSE32393 (n=23) and GSE31979 (n=15), from the Gene Expression Omnibus (GEO) database. For each of the considered datasets, genome-wide DNA methylation was assessed using the Illumina Infinium HumanMethylation27 Beadchip, which profiles the methylation status of ∼27,000 CpG loci, associated with & gt;14,000 genes. Associations between DNA methylation and age were examined by fitting a series of linear regression models to arcsine square root transformed average beta values for all CpG loci in both data sets. Between these data sets, 204 CpG loci were significantly and consistently associated (P & lt; 0.05) with subject age. Relative to the distribution of CpG loci on the array, we observed a significant enrichment of age-related DNA methylation patterns at CpG loci residing in CpG islands (P = 8.7e-6). Further, compared to non-island CpGs, loci in CpG islands were significantly more likely to exhibit increased age-related methylation (P = 0.008). To validate observed age-related DNA methylation, we performed bisulfite pyrosequencing of selected CpGs in an independent set of normal breast tissues (n=20) obtained through the National Disease Research Interchange. Our findings demonstrate consistent age-related methylation changes in normal breast tissue that may represent early events contributing to breast carcinogenesis and additional investigation for enrichment of local sequence and bioinformatic features near CpGs with age-related methylation is ongoing. This work contributes to the understanding of epigenetic mechanisms by which age serves as a major risk factor in the development of breast cancer. Citation Format: Kevin C. Johnson, Amanda K. Jensen, Megan A. Murphy, Devin C. Koestler, Brock C. Christensen. Age-related DNA methylation in normal breast tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3640. doi:10.1158/1538-7445.AM2013-3640
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-3640
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 3
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    DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 9 ( 2011-03-20), p. 1133-1139
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 9 ( 2011-03-20), p. 1133-1139
    Abstract: Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility. Methods We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer. Results In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P 〈 .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members. Conclusion These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2010.31.3577
    RVK:
    XA 52760
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
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  • 4
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    Mitochondrial Genomic Backgrounds Affect Nuclear DNA Methylation and Gene Expression
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 22 ( 2017-11-15), p. 6202-6214
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 22 ( 2017-11-15), p. 6202-6214
    Abstract: Mitochondrial DNA (mtDNA) mutations and polymorphisms contribute to many complex diseases, including cancer. Using a unique mouse model that contains nDNA from one mouse strain and homoplasmic mitochondrial haplotypes from different mouse strain(s)—designated Mitochondrial Nuclear Exchange (MNX)—we showed that mtDNA could alter mammary tumor metastasis. Because retrograde and anterograde communication exists between the nuclear and mitochondrial genomes, we hypothesized that there are differential mtDNA-driven changes in nuclear (n)DNA expression and DNA methylation. Genome-wide nDNA methylation and gene expression were measured in harvested brain tissue from paired wild-type and MNX mice. Selective differential DNA methylation and gene expression were observed between strains having identical nDNA, but different mtDNA. These observations provide insights into how mtDNA could be altering epigenetic regulation and thereby contribute to the pathogenesis of metastasis. Cancer Res; 77(22); 6202–14. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-17-1473
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 5
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    Abstract 4240: A novel approach to adjust for immune cell distribution in blood-based epigenome-wide association studies of cancer.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4240-4240
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4240-4240
    Abstract: Epigenome-wide association studies (EWAS) promise to advance our understanding of epigenetic variation in cancer and are made possible by the recent emergence of cost-effective high-throughput technologies. Blood is the most widely available source of genomic DNA that can be used for study of cancer-associated alterations in DNA methylation (DNAm). These analyses are complicated by the heterogeneity of blood, which represents multiple cell types with unique DNAm signatures. Shifts in immune profile could confound results since altered leukocyte numbers are common in response to exposures or disease. We applied a novel approach to blood-based EWAS, adjusting for leukocyte composition estimated by epigenetic deconvolution of blood. Normal human peripheral blood leukocytes (n = 47) were isolated by magnetic activated cell sorting and purity was confirmed by fluorescence activated cell sorting. DNAm was interrogated using the Infinium HumanMethylation27 BeadArray (Illumina) on the sorted leukocyte samples and peripheral blood samples from 3 independent case-control studies of bladder cancer (223 cases, 205 controls), head and neck squamous cell carcinoma (HNSCC; 92 cases, 92 controls), and ovarian cancer (131 cases, 274 controls). Differentially methylated loci associated with leukocyte lineage were identified using a series of linear mixed effects models fit to the DNAm data for each of the 26,486 autosomal CpGs for the sorted leukocytes, yielding an F-statistic for each locus. The subject-specific leukocyte distribution (vector ω) was estimated using constrained projections, as previously described by Houseman et al (2012). Several regression parameters were estimated: βj, representing the association of case-status and DNAm at CpG j, unadjusted for ω; αj, representing the corresponding association adjusted for ω, and Γ, the association of case-status and ω. Γ, β and α were each adjusted for age, sex and smoking for bladder cancer and HNSCC, and age for ovarian cancer. Statistical inference was achieved by permutation, where null distributions were obtained by permuting case-status with respect to DNAm values and other covariates, using an omnibus test adjusted for multiple-comparisons, constructed by comparing the observed average F-statistic across all CpGs to the corresponding quantity obtained from the permutation distribution. After adjusting for leukocyte composition (α), the association between DNAm and case-status was significant for all 3 studies (bladder cancer: p = 0.047; HNSCC: p = 0.013; ovarian cancer: p = 0.0002). Subsequent analyses revealed that cancer-associated pathways were overrepresented among significant loci. These results indicate cancer-specific variation in DNAm of peripheral blood, independent of immune cell shifts. Further research is indicated for elucidation of mechanisms driving these observations. Citation Format: Scott M. Langevin, E. A. Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Heather H. Nelson, Margaret R. Karagas, Carmen J. Marsit, John K. Wiencke, Karl T. Kelsey. A novel approach to adjust for immune cell distribution in blood-based epigenome-wide association studies of cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4240. doi:10.1158/1538-7445.AM2013-4240
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-4240
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 6
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    Abstract 260: Integrative genomic analysis identifies epigenetic marks that mediate genetic risk for epithelial ovarian cancer
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 260-260
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 260-260
    Abstract: Both genetic and epigenetic factors influence the development and progression of epithelial ovarian cancer (EOC). However, there is an incomplete understanding of the interrelationship between these factors and whether they interact to impact disease risk. Given that the development of ovarian cancer is complex, we aimed to identify DNA methylation marks that are candidates for mediating ovarian cancer genetic risk. We used 214 cases and 214 age-matched controls from the Mayo Clinic Ovarian Cancer Study. Pretreatment, blood-derived DNA was profiled for genome-wide methylation (Illumina Infinium HumanMethylation27 BeadArray) and single nucleotide polymorphisms (SNPs, Illumina Infinium HD Human610-Quad BeadArray). We employed a three-step filtering procedure, followed by the Causal Inference Test (CIT), to distinguish CpG sites that mediate genetic risk, from those that are consequential or independently acted on by genotype. Controlling for the estimated distribution of immune cells and other key covariates, we identified 1,993 out of 25,926 (7.7%) CpGs that were significantly differentially methylated between cases and controls (FDR, q & lt; 0.05). The relationship between methylation and case-control status among these 1,993 CpGs was found to be highly consistent with the results of an independent study. Implementation of the CIT test revealed 13 CpG/SNP pairs, comprising 13 unique CpGs and 17 unique SNPs, which represent potential methylation-mediated relationships between genotype and EOC risk. These findings provide additional insight into EOC etiology and may serve as novel biomarkers for EOC susceptibility. Citation Format: Devin C. Koestler, Prabhakar Chalise, Mine S. Cicek, Julie M. Cunningham, Sebastian Armasu, Melissa C. Larson, Jeremy Chien, Matthew Block, Kimberly R. Kalli, Thomas A. Sellers, Ellen L. Goode, Brooke L. Fridley. Integrative genomic analysis identifies epigenetic marks that mediate genetic risk for epithelial ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 260. doi:10.1158/1538-7445.AM2014-260
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-260
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 7
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    Abstract 830: DNA methylation cytometry reveals cancer survival related to cell composition
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 830-830
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 830-830
    Abstract: Tumor microenvironments are heterogeneous and include epithelial cells, stroma, blood vessels and leukocytes. The interactions between normal and tumor epithelial cells result in responses including angiogenesis, immune regulation and tumor growth. Although flow cytometry and single cell sequencing have been used to investigate cellular composition in tumors, these approaches are dependent upon appropriate substrates that may not be routinely available. Recently, the use of molecular markers of cell type from mRNA (CIBERSORT) and DNA methylation (MethylCIBERSORT) have been used to infer specific cell proportions in tumors. Immune cell type DNA methylation signatures have been well-established for whole blood deconvolution but a challenge in tumors is the potential for carcinoma cells to have signal closely related to nontumor epithelial cells, and heterogeneity of potential tumor distinguishing deconvolution biomarkers. We aim to offer an alternative reference-based approach for tumor deconvolution with DNA methylation using ten normal cell components that we apply to TCGA tumor samples and test the relation of sample composition with patient survival. Ten magnetic sorted cell types with Illumina EPIC DNA methylation data were used as references (B cells, CD4T, CD8T and NK, monocytes, neutrophils, eosinophils, epithelial, endothelial and stromal cells). In total 1256 CpGs were selected for the reference library which was applied to deconvolute 17 TCGA tumor types (n=6417: BLCA, BRCA, COAD, CESC, ESCA, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, PAAD, PRAD, SKCM, STAD, THCA, UCEC). The most abundant cells were epithelial (median:36.6%), endothelial (median: 17.1%), CD8T (median: 12.1%) stromal cells (median:10.3%), and CD4T (median: 4.4%). We calculated three cell ratios: CD8T to epithelial (CD8T:epith), CD4T to epithelial (CD4T:epith) and endothelial to epithelial cells (vasc:epith) and fit Cox proportional hazards models stratified by cancer stage (I, II, III and IV), and adjusted for sex, age at diagnosis, and the three ratios. For all cancers, increased CD8T:epith was associated with worse survival HR: 1.39 (95%CI: 1.15, 1.68). For KIRC, increased CD8T:epith increased the risk of death HR: 1.54 (95%CI: 1.06, 2.22), whereas survival was improved for BRCA HR: 0.15 (95%CI: 0.03, 0.68), and CESC HR: 0.19 95%CI: 0.04, 0.90. A strong effect of increased vasc:epith ratio on risk of death was observed in BLCA HR: 8.03 (95%CI: 3.01, 21.4), and the CD4T:epith ratio reduced the risk of death HR: 0.11 95%CI: 0.02, 0.56. DNA methylation deconvolution is a promising tool for cancer prognosis and offers several technical and cost advantages. However, additional work to further stratify leukocyte signals by cell state such as CD8 T-cell exhaustion, and CD4T Treg infiltration is required. Citation Format: Lucas A. Salas, Karl T. Kelsey, Devin C. Koestler, John K. Wiencke, Brock C. Christensen. DNA methylation cytometry reveals cancer survival related to cell composition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 830.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-830
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 8
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    Abstract 2836: Mitochondrial genomic backgrounds differentially affect nuclear DNA methylation and gene expression
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2836-2836
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2836-2836
    Abstract: Accumulating data implicate mitochondrial genetics and metabolism as contributors to metastatic efficiency. With only 13 proteins encoded by the mtDNA genome, the mechanism(s) by which the coordination of multiple genes involved in metastasis could occur is unclear. We hypothesized that mitochondrial DNA (mtDNA) polymorphisms would differentially regulate nuclear DNA (nDNA) methylation and gene expression. To test the hypotheses, we created Mitochondrial Nuclear Exchange (MNX) mice, by transferring an oocyte nucleus from strainx into an enucleated oocyte from strainy. The mice show that mammary tumor formation and metastasis are regulated by inherited mitochondrial polymorphisms (PMID: 26471915). Age-matched, male mouse brains were collected and pooled from four litter mates representing each of the wild-type and MNX mice (8 groups). Genome-wide nDNA methylation (Mouse methyl-Seq) and gene expression (RNA-Seq) were measured and results validated in independent replicate samples. Significant, selective and reproducible differential DNA methylation and gene expression were observed and validated between strains having identical nDNA, but different mtDNA. While the signal(s) from mitochondria altering methylation is not fully defined, the findings support the hypothesis and demonstrate how mitochondrial genetic alterations could be one of several quantitative trait loci involved in complex phenotypes, such as metastasis. The results also suggest that mtDNA polymorphisms could serve as predictive biomarkers for cancer aggressiveness. Support: Susan G. Komen for the Cure (SAC11037), Natl Fndn Cancer Res, Biomedical Research Training Program, Kansas Bioscience Authority, CA134981, P30-CA168524. Citation Format: Carolyn J. Vivian, Amanda E. Brinker, Stefan Graw, Devin C. Koestler, Christophe Legendre, Gerald C. Gooden, Bodour Salhia, Danny R. Welch. Mitochondrial genomic backgrounds differentially affect nuclear DNA methylation and gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2836. doi:10.1158/1538-7445.AM2017-2836
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-2836
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 9
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    Abstract 878: DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 878-878
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 878-878
    Abstract: Although much is known about molecular and chromosomal characteristics that distinguish glioma histologic subtypes, DNA methylation patterns of gliomas and their association with mutation of isocitrate dehydrogenase (IDH) genes has only recently begun to be investigated. We measured DNA methylation of glioblastomas, astrocytomas, oligodendrogliomas, oligoastrocytomas, ependymomas, and pilocytic astrocytomas (n = 131) from the Brain Tumor Research Center at UCSF, as well as non-tumor brain tissues (n = 7), with the Illumina GoldenGate methylation array. Methylation data were subjected to recursively partitioned mixture modeling (RPMM) to derive methylation classes. Next, differential DNA methylation between tumor and non-tumor was assessed. RPMM was again used to model methylation data for tumors with IDH mutation data (n = 95). Associations between IDH mutation and survival were also examined. Among all gliomas (n = 131), RPMM resulted in eleven methylation classes, and there was a statistically significant association between methylation class and glioma histologic subtype (P & lt; 2.2 × 10−16). Comparing non-tumor brain tissues to gliomas to investigate differential methylation, glioblastomas showed a low ratio of hyper- to hypomethylated loci (ratio = 1.3) compared with the ratio for astrocytomas, oligoastrocytomas, and oligodendrogliomas (ratios = 3.7, 7.6, and 9.7, respectively). Ependymomas had increased hypomethylation (ratio = 0.3). These ratios were significantly different across glioma subtypes (Permutation P & lt; .0001). Assessing IDH1 and IDH2 mutation (IDH), 59% of gliomas had an IDH mutation. IDH mutation was more common in oligoastrocytomas, oligodendrogliomas, or astrocytomas than in glioblastomas, pilocytic astrocytomas, or ependymomas (P = 6.4 × 10−9); in lower-grade tumors (P = .01); in tumors with TP53 mutation (P = .06); and in younger patients (P = .0009). In addition, patients whose tumors harbored mutant IDH had significantly improved survival (HR = 0.27, 95% CI = 0.10 to 0.72). In tumors with available IDH mutation data, RPMM resulted in nine methylation classes, methylation class was significantly associated with IDH mutation (P = 3.0 × 10−16), and this association remained significant when controlling for patient age and tumor histology (likelihood ratio P & lt; .0001). Only two methylation classes contained tumors with IDH mutation, and they had a homogeneous, hypermethylation-rich character compared to the methylation classes for tumors with wild-type IDH. The homogeneity of methylation classes for gliomas with IDH mutation, despite their histologic diversity, strongly suggests that IDH mutation “drives” the observed hypermethylated phenotype, irrespective of tumor histology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 878. doi:10.1158/1538-7445.AM2011-878
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-878
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 10
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    Abstract 5022: Immune biology drives cancer specific methylation profiles in blood
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5022-5022
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5022-5022
    Abstract: Blood leukocytes from patients with solid tumors exhibit complex and distinct cancer-associated patterns of DNA methylation. However, the biological mechanisms underlying these patterns remain poorly understood. Since epigenetic biomarkers offer significant clinical potential for cancer detection, we sought to address a mechanistic gap in recently published works, hypothesizing that this variation is in large part due to shifts in leukocyte populations. To discern differentially methylated regions (DMRs) among leukocyte subtypes, we assessed epigenome-wide DNA methylation in sorted, purified, healthy human peripheral blood leukocyte subtypes. Performing a targeted analysis of leukocyte DMRs from epigenome-wide blood methylation data in three independent case-control studies of different cancers revealed that leukocyte DMRs predict case status with a high degree of accuracy (area under the curve = 0.82, 0.83, and 0.67, forhead and neck squamous cell carcinoma (HNSCC), ovarian, and bladder cancer, respectively). These results demonstrate that blood-derived differences in DNA methylation patterns in patients with solid tumors are largely attributable to systematic differences in the DMRs that define specific, known leukocyte sub-populations, suggesting that the unique epigenetic signatures in blood from solid tumor patients arise as a result of immune responses represented by shifts in leukocyte populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5022. doi:1538-7445.AM2012-5022
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-5022
    RVK:
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    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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