PMID- 12584572
OWN - NLM
STAT- MEDLINE
DCOM- 20030303
LR  - 20051117
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 22
IP  - 6
DP  - 2003 Feb 13
TI  - CpG island methylation in carcinoid and pancreatic endocrine tumors.
PG  - 924-34
AB  - Carcinoid tumors and pancreatic endocrine tumors (PETs) are uncommon 
      neuroendocrine neoplasms and their genetic alterations are not well 
      characterized. CpG island methylation is a mechanism of gene silencing, and 
      concordant methylation of multiple CpG islands as CpG island methylator phenotype 
      (CIMP) has been described in tumors. The aim of this study was to evaluate CIMP 
      in carcinoid tumors and PETs. We studied 16 carcinoid tumors, 11 PETs, and 22 
      associated normal mucosa or pancreas. Methylation status of the p14, p16, 
      cyclo-oxygenase 2 (COX2), O(6)-methyl-guanine methyltransferase (MGMT), estrogen 
      receptor (ER), thrombospondin 1 (THBS1), retinoic acid receptor beta 2 (RARbeta), 
      T-type calcium channel (CACNA1G), and multiple endocrine neoplasia type-1 (MEN1) 
      genes, and of MINT1, MINT2, MINT25, MINT27 and MINT31 loci was evaluated by 
      methylation-specific-PCR (MSP) or combined bisulfite restriction analysis 
      (COBRA). Carcinoid tumors were frequently methylated at RARbeta, MGMT, p16, COX2, 
      p14, THBS1, and ER ranging from 25 to 63% of tumors. Other CpG islands were 
      infrequently methylated or unmethylated. The adjoining normal mucosa was also 
      methylated for ER, COX2, and RARbeta, but methylation at p14, p16, THBS1, and 
      MGMT was tumor-specific. By contrast, PETs and normal pancreas were frequently 
      methylated only at ER. Methylation was more frequent in carcinoid tumors than 
      PETs at MGMT (25 versus 0%, p = 0.03), THBS1 (44 versus 9%, p = 0.04), p14 (44 
      versus 9%, p = 0.04) and RARbeta (25 versus 0%, p = 0.03). Loss of p16 protein 
      expression correlated with methylation of p16 gene in carcinoid tumors (p = 
      0.006). Our study indicates that methylation profile of carcinoid tumors differs 
      from PETs, reflecting different molecular pathogenesis.
FAU - Chan, Annie On-On
AU  - Chan AO
AD  - Department of Pathology, The University of Texas M D Anderson Cancer Center, 
      Houston 77030, USA.
FAU - Kim, Sang Geol
AU  - Kim SG
FAU - Bedeir, Ahmed
AU  - Bedeir A
FAU - Issa, Jean-Pierre
AU  - Issa JP
FAU - Hamilton, Stanley R
AU  - Hamilton SR
FAU - Rashid, Asif
AU  - Rashid A
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoid Tumor/genetics/*metabolism
MH  - Chromosomes, Human, Pair 9
MH  - CpG Islands/*physiology
MH  - Cytoskeletal Proteins/genetics
MH  - *DNA Methylation
MH  - Female
MH  - Genes, p16
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Proteins/genetics
MH  - Pancreatic Neoplasms/genetics/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Sequence Analysis, DNA
MH  - Sequence Deletion
MH  - Trans-Activators/genetics
MH  - beta Catenin
EDAT- 2003/02/14 04:00
MHDA- 2003/03/04 04:00
CRDT- 2003/02/14 04:00
PHST- 2003/02/14 04:00 [pubmed]
PHST- 2003/03/04 04:00 [medline]
PHST- 2003/02/14 04:00 [entrez]
AID - 1206123 [pii]
AID - 10.1038/sj.onc.1206123 [doi]
PST - ppublish
SO  - Oncogene. 2003 Feb 13;22(6):924-34. doi: 10.1038/sj.onc.1206123.