PMID- 12376481
OWN - NLM
STAT- MEDLINE
DCOM- 20021122
LR  - 20190513
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 23
IP  - 10
DP  - 2002 Oct
TI  - Detection of multiple gene hypermethylation in the development of esophageal 
      squamous cell carcinoma.
PG  - 1713-20
AB  - Abnormal hypermethylation of CpG islands associated with tumor suppressor genes 
      can lead to repression of gene expression and contribute significantly to 
      tumorigenesis. Esophageal squamous cell carcinoma (ESCC) is thought to be 
      developed through a multi-stage process, which involves basal cell hyperplasia 
      (BCH), dysplasia (DYS), carcinoma in situ (CIS) and carcinoma. In the present 
      study, we studied the hypermethylation of 10 selected genes in biopsies from 
      normal individuals and resected tissues from ESCC patients. Tumor and neighboring 
      normal and precancerous tissues including BCH, DYS and CIS were microdissected 
      from the resected tissues by laser capture microdissection. Hypermethylation of 
      CpG islands was examined in these samples for 10 genes: p16(INK4a), p15(INK4b), 
      p14(ARF), human leukocyte antigen (HLA)-A, -B, -C, hMLH1, E-cadherin (E-cad), 
      fragile histidine triad and von Hippel-Lindau (VHL). Methylation of two Alu 
      sequences, which neighbor E-cad and VHL, respectively, was used as control to 
      verify the procedure of DNA extraction and chemical modification. In 48 biopsy 
      samples with BCH or DYS, the most frequent hypermethylated genes were p16(INK4a) 
      (18.8%) and p14(ARF) (14.6%). Seventeen out of these 48 samples (35.4%) contained 
      hypermethylation of at least one gene. In the resected tissues, 52% of the BCH 
      and 81% of the tumors showed hypermethylation of at least one gene. Genes 
      hypermethylated in earlier stage lesions were always found hypermethylated at the 
      later stage lesions in the same patient. All of the genes were methylated at some 
      stages and they were clustered into four groups according to their frequencies. 
      The first group of genes, which consisted of p16(INK4a) and p14(ARF), was most 
      frequently hypermethylated in all stages, and the frequencies increased from 
      normal epithelial (0%) to BCH, to displasia/carcinoma in situ and ESCC. Other 
      genes were hypermethylated less frequently. Our results suggest that 
      hypermethylation of key genes, such as p16(INK4a), p14(ARF) and hMLH1, may be 
      used in combination with other molecular changes, such as p53 mutation, in the 
      development of biomarkers for predicting the risk for ESCC.
FAU - Nie, Yan
AU  - Nie Y
AD  - Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical 
      Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New 
      Jersey, Piscataway, NJ 08854-8020, USA.
FAU - Liao, Jie
AU  - Liao J
FAU - Zhao, Xin
AU  - Zhao X
FAU - Song, Yunlong
AU  - Song Y
FAU - Yang, Guang-yu
AU  - Yang GY
FAU - Wang, Li-Dong
AU  - Wang LD
FAU - Yang, Chung S
AU  - Yang CS
LA  - eng
GR  - CA 72030/CA/NCI NIH HHS/United States
GR  - CA65781/CA/NCI NIH HHS/United States
GR  - ES 05022/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (DNA Primers)
SB  - IM
MH  - Base Sequence
MH  - Biopsy
MH  - Carcinoma, Squamous Cell/*genetics/*pathology
MH  - *DNA Methylation
MH  - DNA Primers
MH  - Disease Progression
MH  - Esophageal Neoplasms/*genetics/*pathology
MH  - *Genes/physiology
MH  - Humans
MH  - Hyperplasia
MH  - Kinetics
MH  - Polymerase Chain Reaction
EDAT- 2002/10/12 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/10/12 04:00
PHST- 2002/10/12 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/10/12 04:00 [entrez]
AID - 10.1093/carcin/23.10.1713 [doi]
PST - ppublish
SO  - Carcinogenesis. 2002 Oct;23(10):1713-20. doi: 10.1093/carcin/23.10.1713.