Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression and methylation profile of breast cancer cells.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Francescopaolo Di Cello

PROVIDER: E-GEOD-44838 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer.

Di Cello Francescopaolo F Cope Leslie L Li Huili H Jeschke Jana J Wang Wei W Baylin Stephen B SB Zahnow Cynthia A CA

PloS one 20130703 7

Downregulation of the tight junction protein claudin 1 is a frequent event in breast cancer and is associated with recurrence, metastasis, and reduced survival, suggesting a tumor suppressor role for this protein. Tumor suppressor genes are often epigenetically silenced in cancer. Downregulation of claudin 1 via DNA promoter methylation may thus be an important determinant in breast cancer development and progression. To investigate if silencing of claudin 1 has an epigenetic etiology in breast ...[more]

PMID: 23844228

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Project description:Background an Aim: Epigenetics are thought to play a major role in the carcinogenesis of patients that develop multiple colorectal cancers (CRC) in the non-hereditary setting. Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the underlying epigenetic signature that differentiates multiple from solitary colorectal cancer tumors using a genome-scale DNA methylation profiling. Patients and Methods: We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 age- sex- and tumor location-paired solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significantly hypermethylated CpG sites results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP) using the Infinium DNA methylation data; KRAS and BRAF mutations; microsatellite instability; and immunohistochemistry for MLH1/MSH2/MSH6/PMS2. Functional annotation clustering of differentially methylated genes between multiple and solitary CRCs was performed. Results: We identified 102 CpG sites that showed significant DNA hypermethylation in multiple versus solitary tumors (difference in M-NM-2 value >0.1 and p<0.05). Methylight assays validated the array results for 4 selected significantly hypermethylated genes (MAP1B, HTRA1, ALOX15, TIMP3) identified in the profiling (p=0.0002). Based on the Infinium data, 8/12 (66.6%) of multiple tumors were classified as CIMP-high, as compared to 5/29 (17%) solitary tumors (p=0.004). CIMP-high tumors displayed significant hypermethylation in 301 CpG sites (difference in M-NM-2 value >0.1; p value <0.05). Interestingly, 76/102 (74.5%) of the hypermethylated CpG sites found in multiple vs. solitary tumors were also seen to be hypermethylated in CIMP-H tumors. Functional analysis of hypermethylated genes found in multiple vs. solitary tumors showed the presence and enrichment of genes involved in different tumorigenic functions. Conclusions: Multiple colorectal cancers are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity in the non-hereditary scenario, and provide novel potential biomarkers for identifying high-risk patients and tailoring surveillance strategies. We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay.

Project description:Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in-vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and Quantitative Methylation Specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage-design consisting of Discovery and Prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (k=0.64), HOXA9 (k=0.60), NID2 (k=0.60), and EDNRB (k=0.60) had a moderate to substantial agreement with clinical diagnosis in the Discovery screen. HOXA9 had 68% sensitivity, 100% specificity and a 0.81 AUC. NID2 had 71% sensitivity, 100% specificity and a 0.79 AUC. In the Prevalence screen HOXA9 (k=0.82) and NID2 (k=0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity and a 0.97 AUC. In saliva from OSCC cases and controls HOXA9 had 75% sensitivity, 53% specificity and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity and a 0.73 AUC. This Phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies. The 12 samples analyzed comprise equal numbers of three tissue-types: Primary oral squamous cell carcinoma, Oral leukoplakia and Normal oral mucosa. Gender, age and smoking-status were approximately equally represented in these goups. Normal oral mucosa served as a control.

Dataset Information

Gene expression and methylation profile of breast cancer cells.

Publications

Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer.

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