PMID- 24971511
OWN - NLM
STAT- MEDLINE
DCOM- 20151007
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast 
      cancer.
PG  - e100429
LID - 10.1371/journal.pone.0100429 [doi]
LID - e100429
AB  - The changes in DNA methylation status in cancer cells are characterized by 
      hypermethylation of promoter CpG islands and diffuse genomic hypomethylation. Alu 
      and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic 
      repetitive sequences and methylation of these elements can be used as a surrogate 
      marker for genome-wide methylation status. This study was designed to evaluate 
      the changes of Alu and LINE-1 hypomethylation during breast cancer progression 
      from normal to pre-invasive lesions and invasive breast cancer (IBC), and their 
      relationship with characteristics of IBC. We analyzed the methylation status of 
      Alu and LINE-1 in 145 cases of breast samples including normal breast tissue, 
      atypical ductal hyperplasia/flat epithelial atypia (ADH/FEA), ductal carcinoma in 
      situ (DCIS) and IBC, and another set of 129 cases of IBC by pyrosequencing. Alu 
      methylation showed no significant changes during multistep progression of breast 
      cancer, although it tended to decrease during the transition from DCIS to IBC. In 
      contrast, LINE-1 methylation significantly decreased from normal to ADH/FEA, 
      while it was similar in ADH/FEA, DCIS and IBC. In IBC, Alu hypomethylation 
      correlated with negative estrogen receptor (ER) status, and LINE-1 
      hypomethylation was associated with negative ER status, ERBB2 (HER2) 
      amplification and p53 overexpression. Alu and LINE-1 methylation status was 
      significantly different between breast cancer subtypes, and the HER2 enriched 
      subtype had lowest methylation levels. In survival analyses, low Alu methylation 
      status tended to be associated with poor disease-free survival of the patients. 
      Our findings suggest that LINE-1 hypomethylation is an early event and Alu 
      hypomethylation is probably a late event during breast cancer progression, and 
      prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be 
      related to chromosomal instability of this specific subtype.
FAU - Park, So Yeon
AU  - Park SY
AD  - Department of Pathology, Seoul National University College of Medicine, 
      Jongno-gu, Seoul, Korea; Department of Pathology, Seoul National University 
      Bundang Hospital, Bundang-gu, Seongnam, Gyeonggi, Korea.
FAU - Seo, An Na
AU  - Seo AN
AD  - Department of Pathology, Seoul National University Bundang Hospital, Bundang-gu, 
      Seongnam, Gyeonggi, Korea.
FAU - Jung, Hae Yoen
AU  - Jung HY
AD  - Department of Pathology, Seoul National University Bundang Hospital, Bundang-gu, 
      Seongnam, Gyeonggi, Korea.
FAU - Gwak, Jae Moon
AU  - Gwak JM
AD  - Department of Pathology, Seoul National University College of Medicine, 
      Jongno-gu, Seoul, Korea.
FAU - Jung, Namhee
AU  - Jung N
AD  - Laboratory of Epigenetics, Cancer Research Institute, Seoul National University, 
      Jongno-gu, Seoul, Korea.
FAU - Cho, Nam-Yun
AU  - Cho NY
AD  - Laboratory of Epigenetics, Cancer Research Institute, Seoul National University, 
      Jongno-gu, Seoul, Korea.
FAU - Kang, Gyeong Hoon
AU  - Kang GH
AD  - Department of Pathology, Seoul National University College of Medicine, 
      Jongno-gu, Seoul, Korea; Laboratory of Epigenetics, Cancer Research Institute, 
      Seoul National University, Jongno-gu, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140627
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Alu Elements
MH  - Biomarkers, Tumor
MH  - Breast Neoplasms/diagnosis/*genetics/metabolism/mortality/*pathology
MH  - *DNA Methylation
MH  - Disease Progression
MH  - Epigenesis, Genetic
MH  - Female
MH  - Humans
MH  - *Long Interspersed Nucleotide Elements
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Patient Outcome Assessment
MH  - Phenotype
MH  - Receptor, ErbB-2/*genetics/metabolism
MH  - Young Adult
PMC - PMC4074093
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/28 06:00
MHDA- 2015/10/08 06:00
PMCR- 2014/06/27
CRDT- 2014/06/28 06:00
PHST- 2014/01/02 00:00 [received]
PHST- 2014/05/28 00:00 [accepted]
PHST- 2014/06/28 06:00 [entrez]
PHST- 2014/06/28 06:00 [pubmed]
PHST- 2015/10/08 06:00 [medline]
PHST- 2014/06/27 00:00 [pmc-release]
AID - PONE-D-14-00107 [pii]
AID - 10.1371/journal.pone.0100429 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 27;9(6):e100429. doi: 10.1371/journal.pone.0100429. 
      eCollection 2014.