Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene methylation profile of breast cancer cells.

ABSTRACT: We compared the gene methylation profile of 26 breast cancer cell lines to identify variations associated with different phenotypes and molecular subtype. The panel includes 13 estrogen receptor negative (ER-) and 13 ER+ cell lines. Four of the ER- cell lines and 5 of the ER+ cell lines are HER2 positive. Bisulphite converted DNA from the 26 samples was hybridised to the Illumina Infinium Human Methylation450 Beadchip.

ORGANISM(S): Homo sapiens

SUBMITTER: Francescopaolo Di Cello

PROVIDER: E-GEOD-44837 | 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: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 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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