Deconvolution of DNA methylation identifies differentially methylated gene regions on 1p36 across breast cancer subtypes.

Document Type

Article

Publication Date

9-14-2017

JAX Source

Sci Rep 2017 Sep 14;7(1):11594.

Volume

7

Issue

1

First Page

11594

Last Page

11594

ISSN

2045-2322

PMID

28912426

DOI

https://doi.org/10.1038/s41598-017-10199-z

Abstract

Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized to the chromosomal cytoband 1p36.3. Seventeen of these DMGRs were independently validated in a similar analysis of an external data set. The identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also discuss evidence of the specific importance and potential function of 1p36 in cancer. Sci Rep 2017 Sep 14;7(1):11594.

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