A comprehensive overview of genomic imprinting in breast and its deregulation in cancer.

Nat Commun 2018 10 8;9(1):4120. Epub 2018 Oct 8.

Department Data Analysis and Mathematical Modelling, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.

Genomic imprinting plays an important role in growth and development. Loss of imprinting (LOI) has been found in cancer, yet systematic studies are impeded by data-analytical challenges. We developed a methodology to detect monoallelically expressed loci without requiring genotyping data, and applied it on The Cancer Genome Atlas (TCGA, discovery) and Genotype-Tissue expression project (GTEx, validation) breast tissue RNA-seq data. Here, we report the identification of 30 putatively imprinted genes in breast. In breast cancer (TCGA), HM13 is featured by LOI and expression upregulation, which is linked to DNA demethylation. Other imprinted genes typically demonstrate lower expression in cancer, often associated with copy number variation and aberrant DNA methylation. Downregulation in cancer frequently leads to higher relative expression of the (imperfectly) silenced allele, yet this is not considered canonical LOI given the lack of (absolute) re-expression. In summary, our novel methodology highlights the massive deregulation of imprinting in breast cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-06566-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175939PMC
October 2018
2 Reads

Publication Analysis

Top Keywords

imprinting breast
8
breast cancer
8
genomic imprinting
8
imprinted genes
8
cancer
7
breast
5
upregulation linked
4
expression upregulation
4
loi expression
4
featured loi
4
tcga hm13
4
hm13 featured
4
linked dna
4
demethylation imprinted
4
demonstrate lower
4
lower expression
4
typically demonstrate
4
genes typically
4
cancer tcga
4
dna demethylation
4

Similar Publications