PMID- 28912426
OWN - NLM
STAT- MEDLINE
DCOM- 20190621
LR  - 20210109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Sep 14
TI  - Deconvolution of DNA methylation identifies differentially methylated gene 
      regions on 1p36 across breast cancer subtypes.
PG  - 11594
LID - 10.1038/s41598-017-10199-z [doi]
LID - 11594
AB  - 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.
FAU - Titus, Alexander J
AU  - Titus AJ
AUID- ORCID: 0000-0002-0145-9564
AD  - Program in Quantitative Biomedical Sciences, Geisel School of Medicine at 
      Dartmouth, Hanover, NH, 03755, USA.
AD  - Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, 
      03755, USA.
FAU - Way, Gregory P
AU  - Way GP
AD  - Genomics and Computational Biology Graduate Program, University of Pennsylvania, 
      Philadelphia, PA, 19104, USA.
FAU - Johnson, Kevin C
AU  - Johnson KC
AD  - The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.
AD  - Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, 
      03755, USA.
FAU - Christensen, Brock C
AU  - Christensen BC
AD  - Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, 
      03755, USA. Brock.Christensen@Dartmouth.edu.
AD  - Department of Molecular and Systems Biology, Geisel School of Medicine at 
      Dartmouth, Hanover, NH, 03755, USA. Brock.Christensen@Dartmouth.edu.
AD  - Department of Community and Family Medicine, Geisel School of Medicine at 
      Dartmouth, Hanover, NH, 03755, USA. Brock.Christensen@Dartmouth.edu.
LA  - eng
GR  - UL1 TR001086/TR/NCATS NIH HHS/United States
GR  - R01 DE022772/DE/NIDCR NIH HHS/United States
GR  - T32 LM012204/LM/NLM NIH HHS/United States
GR  - R25 CA134286/CA/NCI NIH HHS/United States
GR  - P20 GM104416/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170914
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Breast Neoplasms/*genetics/*pathology
MH  - *Chromosomes, Human, Pair 1
MH  - Computational Biology/methods
MH  - CpG Islands
MH  - DNA Copy Number Variations
MH  - *DNA Methylation
MH  - Epigenesis, Genetic
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Molecular Sequence Annotation
MH  - Neoplasm Staging
MH  - Promoter Regions, Genetic
MH  - Reproducibility of Results
PMC - PMC5599639
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/16 06:00
MHDA- 2019/06/22 06:00
PMCR- 2017/09/14
CRDT- 2017/09/16 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/08/04 00:00 [accepted]
PHST- 2017/09/16 06:00 [entrez]
PHST- 2017/09/16 06:00 [pubmed]
PHST- 2019/06/22 06:00 [medline]
PHST- 2017/09/14 00:00 [pmc-release]
AID - 10.1038/s41598-017-10199-z [pii]
AID - 10199 [pii]
AID - 10.1038/s41598-017-10199-z [doi]
PST - epublish
SO  - Sci Rep. 2017 Sep 14;7(1):11594. doi: 10.1038/s41598-017-10199-z.