RT Journal Article
SR Electronic
T1 Deconvolution of DNA methylation signatures identifies common differentially methylated gene regions on 1p36 across breast cancer subtypes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 115873
DO 10.1101/115873
A1 Alexander J. Titus
A1 Gregory P. Way
A1 Kevin C. Johnson
A1 Brock C. Christensen
YR 2017
UL http://biorxiv.org/content/early/2017/03/17/115873.1.abstract
AB Breast cancer is a complex disease and studying DNA methylation (DNAm) in tumors is complicated by disease heterogeneity. 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 on each model. 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 on chromosome 1p36.3. We also validated seventeen DMGRs in an independent data set. 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 provide evidence on the importance and potential function of 1p36 in cancer.