RESUMO
The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown. We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized DNA hypomethylation was much more common than hypermethylation and often occurred at putative enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differentiation. The hypomethylated regions strongly overlapped with mapped binding sites of the key neuronal transcription factor NEUROD2. The 5-methylcytosine oxidase ten-eleven translocation 2 (TET2) interacted with NEUROD2, and its reaction product 5-hydroxymethylcytosine accumulated at the demethylated regions. NEUROD2-targeted differentially methylated regions retained higher methylation levels in Neurod2 knockout mice, and inducible expression of NEUROD2 caused TET2-associated demethylation at its in vivo binding sites. The data suggest that the reorganization of DNA methylation in developing neurons involves NEUROD2 and TET2-mediated DNA demethylation.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular , Córtex Cerebral/citologia , Metilação de DNA , Neurônios/citologia , Neuropeptídeos/metabolismo , 5-Metilcitosina/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Proteínas de Ligação a DNA/metabolismo , Dioxigenases , Elementos Facilitadores Genéticos/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurogênese , Motivos de Nucleotídeos/genética , Oxirredução , Ligação Proteica , Proteínas Proto-Oncogênicas/metabolismoRESUMO
PURPOSE: Thyroid cancer is frequently difficult to diagnose due to an overlap of cytologic features between malignant and benign nodules. This overlap leads to unnecessary removal of the thyroid in patients without cancer. While providing some improvement over cytopathologic diagnostics, molecular methods frequently fail to provide a correct diagnosis for thyroid nodules. These approaches are based on the difference between cancer and adjacent thyroid tissue and assume that adjacent tissues are the same as benign nodules. However, in contrast to adjacent tissues, benign thyroid nodules can contain genetic alterations that can be found in cancer.Experimental Design: For the development of a new molecular diagnostic test for thyroid cancer, we evaluated DNA methylation in 109 thyroid tissues by using genome-wide single-base resolution DNA methylation analysis. The test was validated in a retrospective cohort containing 65 thyroid nodules. RESULTS: By conducting reduced representation bisulfite sequencing in 109 thyroid specimens, we found significant differences between adjacent tissue, benign nodules, and cancer. These tissue-specific signatures are strongly linked to active enhancers and cancer-associated genes. Based on these signatures, we developed a new epigenetic approach for thyroid diagnostics. According to the validation cohort, our test has an estimated specificity of 97% [95% confidence interval (CI), 81-100], sensitivity of 100% (95% CI, 87-100), positive predictive value of 97% (95% CI, 83-100), and negative predictive value of 100% (95% CI, 86-100). CONCLUSIONS: These data show that epigenetic testing can provide outstanding diagnostic accuracy for thyroid nodules.See related commentary by Mitmaker et al., p. 457.
Assuntos
Metilação de DNA , Epigênese Genética , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Transcriptoma , Biomarcadores Tumorais , Biópsia por Agulha Fina , Diagnóstico Diferencial , Epigenômica/métodos , Humanos , Mutação , Especificidade de Órgãos , Reação em Cadeia da Polimerase , Análise Serial de Proteínas , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genéticaRESUMO
In a recent paper, we described our efforts in search for evidence supporting epigenetic transgenerational inheritance caused by endocrine disrupter chemicals. One aspect of our study was to compare genome-wide DNA methylation changes in the vinclozolin-exposed fetal male germ cells (n = 3) to control samples (n = 3), their counterparts in the next, unexposed, generation (n = 3 + 3) and also in adult spermatozoa (n = 2 + 2) in both generations. We reported finding zero common hits in the intersection of these four comparisons. In our interpretation, this result did not support the notion that DNA methylation provides a mechanism for a vinclozolin-induced transgenerational male infertility phenotype. In response to criticism by Guerrero-Bosagna regarding our statistical power in the above study, here we provide power calculations to clarify the statistical power of our study and to show the validity of our conclusions. We also explain here how our data is misinterpreted in the commentary by Guerrero-Bosagna by leaving out important data points from consideration.Please see related Correspondence article: xxx (13059_2016_982) and related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0619-z.
Assuntos
Metilação de DNA/genética , Disruptores Endócrinos/toxicidade , Epigênese Genética , Oxazóis/toxicidade , Metilação de DNA/efeitos dos fármacos , Células Germinativas Embrionárias/efeitos dos fármacos , Células Germinativas Embrionárias/metabolismo , Humanos , Masculino , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologiaRESUMO
The tumor suppressor gene RASSF1A is epigenetically silenced in most human cancers. As a binding partner of the kinases MST1 and MST2, the mammalian orthologs of the Drosophila Hippo kinase, RASSF1A is a potential regulator of the Hippo tumor suppressor pathway. RASSF1A shares these properties with the scaffold protein SAV1. The role of this pathway in human cancer has remained enigmatic inasmuch as Hippo pathway components are rarely mutated in tumors. Here we show that Rassf1a homozygous knockout mice develop liver tumors. However, heterozygous deletion of Sav1 or codeletion of Rassf1a and Sav1 produced liver tumors with much higher efficiency than single deletion of Rassf1a. Analysis of RASSF1A-binding partners by mass spectrometry identified the Hippo kinases MST1, MST2, and the oncogenic IκB kinase TBK1 as the most enriched RASSF1A-interacting proteins. The transcriptome of Rassf1a(-/-) livers was more deregulated than that of Sav1(+/-) livers, and the transcriptome of Rassf1a(-/-), Sav1(+/-) livers was similar to that of Rassf1a(-/-) mice. We found that the levels of TBK1 protein were substantially upregulated in livers lacking Rassf1a. Furthermore, transcripts of several ß-tubulin isoforms were increased in the Rassf1a-deficient livers presumably reflecting a role of RASSF1A as a microtubule-stabilizing protein. In human liver cancer, RASSF1A frequently undergoes methylation at the promoter but this was not observed for MST1, MST2, or SAV1. Our results suggest a multifactorial role of RASSF1A in suppression of liver carcinogenesis. Cancer Res; 76(9); 2824-35. ©2016 AACR.
Assuntos
Proteínas de Ciclo Celular/genética , Transformação Celular Neoplásica/genética , Neoplasias Hepáticas/genética , Proteínas Supressoras de Tumor/genética , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/patologia , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Modelos Animais de Doenças , Imunoprecipitação , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Proteínas Supressoras de Tumor/metabolismoRESUMO
Piwi-interacting RNAs (piRNAs) are a distinct group of small noncoding RNAs (sncRNAs) that silence transposable genetic elements to protect genome integrity. Because of their limited expression in gonads and sequence diversity, piRNAs remain the most mysterious class of small RNAs. Studies have shown piRNAs are present in somatic cells and dysregulated in gastric, breast and liver cancers. By deep sequencing 24 frozen benign kidney and clear cell renal cell carcinoma (ccRCC) specimens and using the publically available piRNA database, we found 26,991 piRNAs present in human kidney tissue. Among 920 piRNAs that had at least two copies in one specimen, 19 were differentially expressed in benign kidney and ccRCC tissues, and 46 were associated with metastasis. Among the metastasis-related piRNAs, we found three piRNAs (piR-32051, piR-39894 and piR-43607) to be derived from the same piRNA cluster at chromosome 17. We confirmed the three selected piRNAs not to be miRNAs or miRNA-like sncRNAs. We further validated the aberrant expression of the three piRNAs in a 68-case formalin-fixed and paraffin-embedded (FFPE) ccRCC tissue cohort and showed the up-regulation of the three piRNAs to be highly associated with ccRCC metastasis, late clinical stage and poor cancer-specific survival.
Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , RNA Interferente Pequeno/genética , Idoso , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Genômica , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Família Multigênica , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Exposure to environmental endocrine-disrupting chemicals during pregnancy reportedly causes transgenerationally inherited reproductive defects. We hypothesized that to affect the grandchild, endocrine-disrupting chemicals must alter the epigenome of the germ cells of the in utero-exposed G1 male fetus. Additionally, to affect the great-grandchild, the aberration must persist in the germ cells of the unexposed G2 grandchild. RESULTS: Here, we treat gestating female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during the time when global de novo DNA methylation and imprint establishment occurs in the germ cells of the G1 male fetus. We map genome-wide features in purified G1 and G2 prospermatogonia, in order to detect immediate and persistent epigenetic aberrations, respectively. We detect changes in transcription and methylation in the G1 germline immediately after endocrine-disrupting chemicals exposure, but changes do not persist into the G2 germline. Additional analysis of genomic imprints shows no persistent aberrations in DNA methylation at the differentially methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or in the allele-specific transcription of imprinted genes between the G2 and G3 soma. CONCLUSIONS: Our results suggest that endocrine-disrupting chemicals exert direct epigenetic effects in exposed fetal germ cells, which are corrected by reprogramming events in the next generation. Avoiding transgenerational inheritance of environmentally-caused epigenetic aberrations may have played an evolutionary role in the development of dual waves of global epigenome reprogramming in mammals.
Assuntos
Reprogramação Celular/genética , Metilação de DNA/genética , Epigênese Genética/efeitos dos fármacos , Impressão Genômica/efeitos dos fármacos , Animais , Compostos Benzidrílicos/administração & dosagem , Reprogramação Celular/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Disruptores Endócrinos/administração & dosagem , Feminino , Impressão Genômica/genética , Células Germinativas/efeitos dos fármacos , Masculino , Camundongos , Oxazóis/administração & dosagem , Fenóis/administração & dosagem , Gravidez , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacosRESUMO
Sodium bisulfite-assisted deamination of cytosine forms the basis for conducting single base resolution analysis of 5-methylcytosine in DNA. The TET family of proteins represents a group of enzymes that can oxidize 5-methylcytosine to 5-hydroxymethylcytosine. A modification of the bisulfite-based DNA methylation mapping technique employs TET1-mediated oxidation of 5-methylcytosine (TET-assisted bisulfite sequencing) for single base analysis of 5-hydroxymethylcytosine. Whole genome analysis of cytosine modifications with bisulfite sequencing techniques still is challenging and expensive. Reduced representation bisulfite sequencing (RRBS) has been used to limit the complexity of the analysis to mostly CpG-rich genomic fragments flanked by restriction enzyme cleavage sites, for example MspI (5'CCGG). In this chapter, we describe detailed methods used in our laboratory for analysis of 5-methylcytosine and 5-hydroxymethylcytosine combined (RRBS) and for specific analysis of 5-hydroxymethylcytosine (TAB-RRBS).
Assuntos
5-Metilcitosina/metabolismo , Citosina/análogos & derivados , Análise de Sequência de DNA/métodos , Citosina/metabolismo , Desoxirribonuclease HpaII/metabolismo , Glicosilação , Humanos , Oxirredução , Sulfitos/farmacologiaRESUMO
In colon tumors, the transcription of many genes becomes deregulated by poorly defined epigenetic mechanisms that have been studied mainly in established cell lines. In this study, we used frozen human colon tissues to analyze patterns of histone modification and DNA cytosine methylation in cancer and matched normal mucosa specimens. DNA methylation is strongly targeted to bivalent H3K4me3- and H3K27me3-associated promoters, which lose both histone marks and acquire DNA methylation. However, we found that loss of the Polycomb mark H3K27me3 from bivalent promoters was accompanied often by activation of genes associated with cancer progression, including numerous stem cell regulators, oncogenes, and proliferation-associated genes. Indeed, we found many of these same genes were also activated in patients with ulcerative colitis where chronic inflammation predisposes them to colon cancer. Based on our findings, we propose that a loss of Polycomb repression at bivalent genes combined with an ensuing selection for tumor-driving events plays a major role in cancer progression.
Assuntos
Neoplasias Colorretais/genética , Metilação de DNA , Repressão Epigenética/genética , Histonas/metabolismo , Regiões Promotoras Genéticas/genética , Proliferação de Células , Transformação Celular Neoplásica/genética , Cromatina/genética , Imunoprecipitação da Cromatina , Colite Ulcerativa/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Humanos , Células-Tronco Neoplásicas/citologia , Proteínas do Grupo Polycomb/genética , Transcrição GênicaRESUMO
To understand what dictates the emerging patterns of de novo DNA methylation in the male germline, we mapped DNA methylation, chromatin, and transcription changes in purified fetal mouse germ cells by using methylated CpG island recovery assay (MIRA)-chip, chromatin immunoprecipitation (ChIP)-chip, and strand-specific RNA deep sequencing, respectively. Global de novo methylation occurred by default in prospermatogonia without any apparent trigger from preexisting repressive chromatin marks but was preceded by broad, low-level transcription along the chromosomes, including the four known paternally imprinted differentially methylated regions (DMRs). Default methylation was excluded only at precisely aligned constitutive or emerging peaks of H3K4me2, including most CpG islands and some intracisternal A particles (IAPs). Similarly, each maternally imprinted DMR was protected from default DNA methylation among highly methylated DNA by an H3K4me2 peak and transcription initiation at least in one strand. Our results suggest that the pattern of de novo DNA methylation in prospermatogonia is dictated by opposing actions of broad, low-level transcription and dynamic patterns of active chromatin.
Assuntos
Metilação de DNA , Histonas/metabolismo , Processamento de Proteína Pós-Traducional , Espermatogônias/metabolismo , Animais , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina , Ilhas de CpG , Genoma , Masculino , Camundongos , Espermatócitos/metabolismo , Transcrição GênicaRESUMO
DNA methylation in mammals is highly dynamic during germ cell and preimplantation development but is relatively static during the development of somatic tissues. 5-hydroxymethylcytosine (5hmC), created by oxidation of 5-methylcytosine (5mC) by Tet proteins and most abundant in the brain, is thought to be an intermediary toward 5mC demethylation. We investigated patterns of 5mC and 5hmC during neurogenesis in the embryonic mouse brain. 5hmC levels increase during neuronal differentiation. In neuronal cells, 5hmC is not enriched at enhancers but associates preferentially with gene bodies of activated neuronal function-related genes. Within these genes, gain of 5hmC is often accompanied by loss of H3K27me3. Enrichment of 5hmC is not associated with substantial DNA demethylation, suggesting that 5hmC is a stable epigenetic mark. Functional perturbation of the H3K27 methyltransferase Ezh2 or of Tet2 and Tet3 leads to defects in neuronal differentiation, suggesting that formation of 5hmC and loss of H3K27me3 cooperate to promote brain development.
Assuntos
Cromatina/metabolismo , Citosina/análogos & derivados , Neurogênese , Neurônios/metabolismo , 5-Metilcitosina/análogos & derivados , Animais , Células Cultivadas , Citosina/metabolismo , Metilação de DNA , Proteína Potenciadora do Homólogo 2 de Zeste , Epigenômica , Histonas/genética , Histonas/metabolismo , Camundongos , Neurônios/citologia , Oxirredução , Complexo Repressor Polycomb 2/antagonistas & inibidores , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/metabolismoRESUMO
Unprotected exposure to UVB radiation from the sun and the resulting DNA damage are thought to be responsible for physiological changes in the skin and for a variety of skin cancers, including basal cell and squamous cell carcinoma and malignant melanoma. Although the mutagenic effects of UVB have been well documented and studied mechanistically, there is only limited information as to whether UV light may also be responsible for inducing epigenetic changes in the genome of exposed cells. DNA methylation is a stable epigenetic modification involved in gene control. To study the effects of UVB radiation on DNA methylation, we repeatedly exposed normal human keratinocytes to a UVB light source. After a recovery period, we analyzed global DNA methylation patterns in the irradiated and control cells using the methylated-CpG island recovery assay (MIRA) method in combination with high-resolution microarrays. Bioinformatics analysis revealed only a limited number of possible differences between UVB-exposed and control cells. However, these minor apparent changes could not be independently confirmed by bisulfite sequencing-based approaches. This study reveals that UVB irradiation of keratinocytes has no recognizable global effect on DNA methylation patterns and suggests that changes in DNA methylation, as observed in skin cancers, are not immediate consequences of human exposure to solar UVB irradiation.
RESUMO
Environmental chemicals and radiation have often been implicated in producing alterations of the epigenome thus potentially contributing to cancer and other diseases. Ionizing radiation, released during accidents at nuclear power plants or after atomic bomb explosions, is a potentially serious health threat for the exposed human population. This type of high-energy radiation causes DNA damage including single- and double-strand breaks and induces chromosomal rearrangements and mutations, but it is not known if ionizing radiation directly induces changes in the epigenome of irradiated cells. We treated normal human fibroblasts and normal human bronchial epithelial cells with different doses of γ-radiation emitted from a cesium 137 ((137)Cs) radiation source. After a seven-day recovery period, we analyzed global DNA methylation patterns in the irradiated and control cells using the methylated-CpG island recovery assay (MIRA) in combination with high-resolution microarrays. Bioinformatics analysis revealed only a small number of potential methylation changes with low fold-difference ratios in the irradiated cells. These minor methylation differences seen on the microarrays could not be verified by COBRA (combined bisulfite restriction analysis) or bisulfite sequencing of selected target loci. Our study shows that acute γ-radiation treatment of two types of human cells had no appreciable direct effect on DNA cytosine methylation patterns in exposed cells.
Assuntos
Dano ao DNA/efeitos da radiação , Metilação de DNA/efeitos da radiação , Raios gama , Ilhas de CpG , Relação Dose-Resposta à Radiação , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Humanos , Análise de Sequência de DNARESUMO
To elucidate the relationship between intragenic DNA methylation and chromatin marks, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and in the colorectal cancer cell line HCT116 as well as its counterpart with double knockout of DNMT1 and DNMT3B (HCT116-DKO). Analysis of H3K36me3 profiles indicated that this intragenic mark of active genes is associated with two categories of genes: (i) genes with low CpG density and H3K9me3 in the gene body or (ii) genes with high CpG density and DNA methylation in the gene body. We observed that a combination of low CpG density in gene bodies together with H3K9me3 and H3K36me3 occupancy is a specific epigenetic feature of zinc finger (ZNF) genes, which comprise 90% of all genes carrying both histone marks on chromosome 19. For genes with high intragenic CpG density, transcription and H3K36me3 occupancy were not changed in conditions of partial or intensive loss of DNA methylation in gene bodies. siRNA knockdown of SETD2, the major histone methyltransferase responsible for production of H3K36me3, did not reduce DNA methylation in gene bodies. Our study suggests that the H3K36me3 and DNA methylation marks in gene bodies are established largely independently of each other and points to similar functional roles of intragenic DNA methylation and intragenic H3K9me3 for CpG-rich and CpG-poor genes, respectively.
Assuntos
Cromatina/genética , Cromatina/metabolismo , Metilação de DNA/genética , Histonas/metabolismo , Lisina/metabolismo , Brônquios/citologia , Cromossomos Humanos Par 19/genética , Análise por Conglomerados , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/deficiência , DNA (Citosina-5-)-Metiltransferases/metabolismo , Epigênese Genética , Células Epiteliais/metabolismo , Técnicas de Silenciamento de Genes , Técnicas de Inativação de Genes , Células HCT116 , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Processamento de Proteína Pós-Traducional , Ativação Transcricional , Dedos de Zinco/genética , DNA Metiltransferase 3BRESUMO
Methylation at the 5-position of cytosine is a well-studied epigenetic pathway. In addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) also referred to as the sixth DNA base have been detected in certain tissues, most notably the brain. However, the genomic distribution of this cytosine modification is unknown. Here, we have used an immunoprecipitation technique (5hmC-IP) to examine the occurrence of 5hmC in DNA from human brain frontal lobe tissue. The distribution of 5hmC was compared to that of 5mC. We show that 5hmC is more selectively targeted to genes than is 5mC. 5hmC is particularly enriched at promoters and in intragenic regions (gene bodies) but is largely absent from non-gene regions. 5hmC peaks at transcription start sites did not correlate with gene expression levels for promoters with intermediate or high CpG content. However, the presence of 5hmC in gene bodies was more positively correlated with gene expression levels than was the presence of 5mC. Promoters of testis-specific genes showed strong 5mC peaks in brain DNA but were almost completely devoid of 5hmC. Our data provide an overview of the genomic distribution of 5hmC in human brain and will set the stage for further functional characterization of this novel DNA modification.
Assuntos
Química Encefálica , Citosina/análogos & derivados , DNA/química , 5-Metilcitosina/análise , Animais , Citosina/análise , Expressão Gênica , Genômica , Humanos , Camundongos , Regiões Promotoras GenéticasRESUMO
To reveal the extent of domain-wide epigenetic features at imprinted gene clusters, we performed a high-resolution allele-specific chromatin analysis of over 100 megabases along the maternally or paternally duplicated distal chromosome 7 (Chr7) and Chr15 in mouse embryo fibroblasts (MEFs). We found that reciprocal allele-specific features are limited to imprinted genes and their differentially methylated regions (DMRs), whereas broad local enrichment of H3K27me3 (BLOC) is a domain-wide feature at imprinted clusters. We uncovered novel allele-specific features of BLOCs. A maternally biased BLOC was found along the H19-Igf2 domain. A paternal allele-specific gap was found along Kcnq1ot1, interrupting a biallelic BLOC in the Kcnq1-Cdkn1c domain. We report novel allele-specific chromatin marks at the Peg13 and Slc38a4 DMRs, Cdkn1c upstream region, and Inpp5f_v2 DMR and paternal allele-specific CTCF binding at the Peg13 DMR. Additionally, we derived an imprinted gene predictor algorithm based on our allele-specific chromatin mapping data. The binary predictor H3K9ac and CTCF or H3K4me3 in one allele and H3K9me3 in the reciprocal allele, using a sliding-window approach, recognized with precision the parental allele specificity of known imprinted genes, H19, Igf2, Igf2as, Cdkn1c, Kcnq1ot1, and Inpp5f_v2 on Chr7 and Peg13 and Slc38a4 on Chr15. Chromatin features, therefore, can unequivocally identify genes with imprinted expression.
Assuntos
Cromatina/genética , Cromatina/metabolismo , Cromossomos , Metilação de DNA , Algoritmos , Alelos , Animais , Células Cultivadas , Histonas/metabolismo , Camundongos , Transcrição GênicaAssuntos
Carcinoma de Células Renais/genética , Tumores do Estroma Gastrointestinal/genética , Neoplasias Renais/genética , Linfoma de Célula do Manto/genética , NF-kappa B/genética , Neoplasias Primárias Múltiplas , Transdução de Sinais/genética , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Quimioterapia Adjuvante , Hibridização Genômica Comparativa , Ciclofosfamida/administração & dosagem , Citocinas/sangue , Procedimentos Cirúrgicos do Sistema Digestório , Doxorrubicina/administração & dosagem , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/imunologia , Tumores do Estroma Gastrointestinal/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Neoplasias Renais/diagnóstico , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/imunologia , Linfoma de Célula do Manto/terapia , Masculino , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Women's regular use of mammography over a 6 year interval was examined among women aged 45-75 in the Hawaii and Los Angeles Multiethnic Cohort (MEC). The analyses included 81,722 African American, Japanese, Latina, Native Hawaiian, and White females using self-reported mammography history from 1993 to 1998. Ninety-one percent of MEC women reported ever having a mammogram, however only 36% reported regular annual and 48% reported regular biennial mammography over the interval. Mammography was lowest among women who were obese, had a high school education or less, or who were aged 70 and over. Regular mammography use during follow-up was low compared to prior studies reporting on recent mammography. African American, Latina, and Native Hawaiian women had significantly lower annual and biennial mammography use compared to White women even after controlling for age, education, family history, body mass index and hormone therapy indicating that gaps exist in mammography that remain unexplained by known predictors of screening behavior.