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1. Cancer Inform. 2012;11:61-75. Epub 2012 Mar 12.

Integrated Analysis Reveals hsa-miR-142 as a Representative of a
Lymphocyte-Specific Gene Expression and Methylation Signature.

Andreopoulos B, Anastassiou D.

Center for Computational Biology and Bioinformatics, Department of Electrical
Engineering, Columbia University, New York, NY 10027, USA.

Gene expression profiling has provided insights into different cancer types and
revealed tissue-specific expression signatures. Alterations in microRNA
expression contribute to the pathogenesis of many types of human diseases. Few
studies have integrated all levels of gene expression, miRNA and methylation to
uncover correlations between these data types. We performed an integrated
profiling to discover instances of miRNAs associated with a gene expression and
DNA methylation signature across multiple cancer types. Using data from The
Cancer Genome Atlas (TCGA), we revealed a concordant gene expression and
methylation signature associated with the microRNA hsa-miR-142 across the same
samples. In all cancer types examined, we found a signature of co-expression of a
gene set R and methylated sites M, which correlate positively (M+) or negatively
(M-) with the expression of hsa-miR-142. The set R consistently contains many
genes, such as TRAF3IP3, NCKAP1L, CD53, LAPTM5, PTPRC, EVI2B, DOCK2, LCP2, CYBB
and FYB. The signature is preserved across glioblastoma, ovarian, breast, colon,
kidney, lung, uterine and rectum cancer. There is 28% overlap of methylation
sites in M between glioblastoma (GBM) and ovarian cancer. There is 60% overlap of
genes in R between GBM and ovarian (P = 1.3e(-11)). Most of the genes in R are
known to be expressed in lymphocytes and haematopoietic stem cells, while M
reflects membrane proteins involved in cell-cell adhesion functions. We speculate
that the hsa-miR-142 associated signature may signal haematopoietic-specific
processes and an accumulation of methylation events triggering a progressive loss
of cell-cell adhesion. We also observed that GBM samples belonging to the
proneural subtype tend to have underexpressed hsa-miR-142 and R genes,
hypomethylated M+ and hypermethylated M-, while the mesenchymal samples have the
opposite profile.

PMID: 22570537 [PubMed - in process]