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Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.

Abstract Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%-35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the DNA methylation status. We identified CpG loci and regions consistently hyper-methylated throughout the serrated carcinogenesis spectrum, in both our SSA/P specimens and in serrated cancers. Hyper-methylated CpG loci included the known the tumor suppressor gene RET (p = 5.72 x 10-10), as well as loci in differentially methylated regions for GSG1L, MIR4493, NTNG1, MCIDAS, ZNF568, and RERG. The hyper-methylated loci that we identified help characterize the biology of SSA/P development, and could be useful as therapeutic targets, or for future identification of patients who may benefit from shorter surveillance intervals.
PMID
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Authors

Mayor MeshTerms

DNA Methylation

Keywords

colon cancer

methylation

serrated polyp

sessile serrated adenoma

Journal Title international journal of molecular sciences
Publication Year Start




PMID- 28257124
OWN - NLM
STAT- MEDLINE
DA  - 20170303
DCOM- 20170317
LR  - 20170317
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 3
DP  - 2017 Mar 02
TI  - Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated
      Cancers.
LID - E535 [pii]
LID - 10.3390/ijms18030535 [doi]
AB  - Although serrated polyps were historically considered to pose little risk, it is 
      now understood that progression down the serrated pathway could account for as
      many as 15%-35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P)
      is the most prevalent pre-invasive serrated lesion. Our objective was to identify
      the CpG loci that are persistently hyper-methylated during serrated
      carcinogenesis, from the early SSA/P lesion through the later cancer phases of
      neoplasia development. We queried the loci hyper-methylated in serrated cancers
      within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using
      the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the
      DNA methylation status. We identified CpG loci and regions consistently
      hyper-methylated throughout the serrated carcinogenesis spectrum, in both our
      SSA/P specimens and in serrated cancers. Hyper-methylated CpG loci included the
      known the tumor suppressor gene RET (p = 5.72 x 10-10), as well as loci in
      differentially methylated regions for GSG1L, MIR4493, NTNG1, MCIDAS, ZNF568, and 
      RERG. The hyper-methylated loci that we identified help characterize the biology 
      of SSA/P development, and could be useful as therapeutic targets, or for future
      identification of patients who may benefit from shorter surveillance intervals.
FAU - Andrew, Angeline S
AU  - Andrew AS
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
FAU - Baron, John A
AU  - Baron JA
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
AD  - Department of Medicine, University of North Carolina School of Medicine, Chapel
      Hill, NC 27599, USA. [email protected]
FAU - Butterly, Lynn F
AU  - Butterly LF
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
FAU - Suriawinata, Arief A
AU  - Suriawinata AA
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
FAU - Tsongalis, Gregory J
AU  - Tsongalis GJ
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
FAU - Robinson, Christina M
AU  - Robinson CM
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
FAU - Amos, Christopher I
AU  - Amos CI
AD  - Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 7936 One
      Medical Center Drive, Lebanon, NH 03756, USA. [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170302
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
SB  - IM
MH  - Adenoma/*genetics
MH  - Colonic Polyps/*genetics
MH  - Colorectal Neoplasms/*genetics
MH  - CpG Islands
MH  - *DNA Methylation
MH  - Early Detection of Cancer
MH  - Female
MH  - Genetic Loci
MH  - Humans
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - colon cancer
OT  - methylation
OT  - serrated polyp
OT  - sessile serrated adenoma
EDAT- 2017/03/04 06:00
MHDA- 2017/03/18 06:00
CRDT- 2017/03/04 06:00
PHST- 2017/01/03 [received]
PHST- 2017/02/22 [accepted]
AID - ijms18030535 [pii]
AID - 10.3390/ijms18030535 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Mar 2;18(3). pii: E535. doi: 10.3390/ijms18030535.

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