Project description:Purpose: Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design: Discovery phase utilized the Illumina Golden Gate Cancer Panel I in 51 OLD and 6 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-1, were further validated in an independent sample set consisting in 160 OLD and 65 controls. Results: DNA methylation profiles of the OLD showed only minor significant differences when compared to controls. Conclusions: In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder. Bisulphite-converted DNA from the 51 oral lichenoid disease samples and 6 control samples were hybridised to the Illumina GoldenGate Methylation Cancer Panel I.
Project description:Objectives: Earlier studies involving a priori gene selection have identified promoter regions deregulated by DNA methylation changes in oral squamous cell cancers (OSCCs) and precancers. Interrogation of global DNA methylation patterns for such specimens has not been reported, though such analyses are needed to uncover novel molecular factors driving disease. Materials and Methods: We evaluated global DNA methylation patterns for 30 biopsies obtained from 10 patients undergoing surgical removal of an OSCC or carcinoma in situ (CIS). From a disease field in each patient, we collected i) dysplastic, ii) CIS or OSCC, and iii) adjacent normal biopsies. DNA isolated from each biopsy was profiled for methylation status using the Illumina HumanMethylation27K platform. Results: Our data demonstrate that aberrant methylation of promoter CpG islands exists across oral precancer and OSCC genomes. Non-hierarchical clustering of all methylation data revealed distinct methylation patterns between the normal and the CIS/OSCC tissues (with results for dysplastic biopsies split between groups). Multiple genes exhibiting recurrent aberrant DNA methylation were found for both dysplastic and CIS/OSCC groups, and included enrichment for genes found in the WNT and MAPK signaling pathways. Conclusion: In identifying aberrant DNA methylation at the earliest stages of oral precancer and finding recurring epigenetic disruption of specific genes/pathways across our analyzed cohort, we conclude that CpG methylation changes are a hallmark of oral cancer progression and that global DNA methylation analyses are an essential component for wider studies seeking to derive biomarkers or potentially druggable targets for improving oral cancer outcomes. Bisulphite converted DNA from the 30 samples were hybridised to the Illumina Infinium 27k Human Methylation BeadChip v1.2. Total RNA from 30 oral cancer samples were hybridized to Agilent 4x44k gene expression microarray.
Project description:Purpose: Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design: Discovery phase utilized the Illumina Golden Gate Cancer Panel I in 51 OLD and 6 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-1, were further validated in an independent sample set consisting in 160 OLD and 65 controls. Results: DNA methylation profiles of the OLD showed only minor significant differences when compared to controls. Conclusions: In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder.
Project description:Purpose Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design Discovery phase utilized HumanMethylation27 DNA Analysis BeadChip assay in 18 OLD and 5 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-, were further validated in an independent sample set consisting in 158 OLD and 65 controls. Results DNA methylation profile of the OLD showed only minor significant differences when compared to controls. MGC40178, ADORA1 and LINE-1 were slightly hypomethylated in 23, 40 and 43 % of the OLD samples respectively, while only in 13, 18 and 15% of the controls. Conclusions In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder. Bisulphite converted DNA from the 17 Oral lichenoid samples and 5 control samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.217
Project description:Objectives: Earlier studies involving a priori gene selection have identified promoter regions deregulated by DNA methylation changes in oral squamous cell cancers (OSCCs) and precancers. Interrogation of global DNA methylation patterns for such specimens has not been reported, though such analyses are needed to uncover novel molecular factors driving disease. Materials and Methods: We evaluated global DNA methylation patterns for 30 biopsies obtained from 10 patients undergoing surgical removal of an OSCC or carcinoma in situ (CIS). From a disease field in each patient, we collected i) dysplastic, ii) CIS or OSCC, and iii) adjacent normal biopsies. DNA isolated from each biopsy was profiled for methylation status using the Illumina HumanMethylation27K platform. Results: Our data demonstrate that aberrant methylation of promoter CpG islands exists across oral precancer and OSCC genomes. Non-hierarchical clustering of all methylation data revealed distinct methylation patterns between the normal and the CIS/OSCC tissues (with results for dysplastic biopsies split between groups). Multiple genes exhibiting recurrent aberrant DNA methylation were found for both dysplastic and CIS/OSCC groups, and included enrichment for genes found in the WNT and MAPK signaling pathways. Conclusion: In identifying aberrant DNA methylation at the earliest stages of oral precancer and finding recurring epigenetic disruption of specific genes/pathways across our analyzed cohort, we conclude that CpG methylation changes are a hallmark of oral cancer progression and that global DNA methylation analyses are an essential component for wider studies seeking to derive biomarkers or potentially druggable targets for improving oral cancer outcomes.
Project description:Purpose Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design Discovery phase utilized HumanMethylation27 DNA Analysis BeadChip assay in 18 OLD and 5 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-, were further validated in an independent sample set consisting in 158 OLD and 65 controls. Results DNA methylation profile of the OLD showed only minor significant differences when compared to controls. MGC40178, ADORA1 and LINE-1 were slightly hypomethylated in 23, 40 and 43 % of the OLD samples respectively, while only in 13, 18 and 15% of the controls. Conclusions In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder.
Project description:This SuperSeries is composed of the following subset Series: GSE42044: DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (sequencing) GSE42118: DNA methylation changes are a late event in Acute Promyelocytic Leukemia and coincide with loss of transcription factor binding (Illumina Methylation) Refer to individual Series
Project description:Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies. 15 samples. HpaII libraries were compared to at least 3 MspI libraries from the same sample