PMID- 12800194
OWN - NLM
STAT- MEDLINE
DCOM- 20030807
LR  - 20171116
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 106
IP  - 2
DP  - 2003 Aug 20
TI  - Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast 
      cancer.
PG  - 198-204
AB  - TMS1 (target of methylation-induced silencing) is a CpG island-associated gene 
      that functions in the regulation of apoptosis and encodes a caspase recruitment 
      domain, a recently described motif found in apoptotic signaling molecules. Recent 
      evidence suggests that silencing of genes in the apoptotic pathway contribute to 
      human carcinogenesis. We examined the DNA methylation status of the TMS1 promoter 
      in lung and breast tumor tissues, tumor cell lines and nonmalignant tissues by 
      methylation-specific polymerase chain reaction (MSP) and its mRNA expression by 
      reverse transcription PCR. Aberrant methylation of TMS1 was present in 70% (40 of 
      57) of small cell lung cancer (SCLC) cell lines and 41% (13 of 32) of SCLC tumor 
      tissues, 48% (29 of 61) of non small cell lung cancer (NSCLC) cell lines and 40% 
      (28 of 70) of NSCLC tumor tissues and 46% (12 of 26) of breast cancer cell lines 
      and 32% (20 of 63) of breast tumor tissues. Methylation was absent in the 
      peripheral blood lymphocytes and buccal epithelium from healthy volunteers, as 
      well as in nonmalignant lung tissues and was rare in nonmalignant breast tissues 
      7% (2 of 30). DNA methylation was confirmed by sequence analysis and the 
      methylation status correlated inversely with TMS1 RNA expression in 18 cell lines 
      tested. RNA expression was restored by treatment with the demethylating agent 
      5-aza-2'-deoxycytidine, in 4 of 4 methylated cell lines that lacked the TMS1 
      transcript. Our results suggest that methylation of TMS1 may play a role in the 
      pathogenesis of small cell and non small lung and breast cancers.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Virmani, Arvind
AU  - Virmani A
AD  - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern 
      Medical Center, Dallas, TX, USA. arvind@geneticassays.com
FAU - Rathi, Asha
AU  - Rathi A
FAU - Sugio, Kenji
AU  - Sugio K
FAU - Sathyanarayana, Ubaradka G
AU  - Sathyanarayana UG
FAU - Toyooka, Shinichi
AU  - Toyooka S
FAU - Kischel, Frank C
AU  - Kischel FC
FAU - Tonk, Vijay
AU  - Tonk V
FAU - Padar, Asha
AU  - Padar A
FAU - Takahashi, Takashi
AU  - Takahashi T
FAU - Roth, Jack A
AU  - Roth JA
FAU - Euhus, David M
AU  - Euhus DM
FAU - Minna, John D
AU  - Minna JD
FAU - Gazdar, Adi F
AU  - Gazdar AF
LA  - eng
GR  - 2R01CA71618/CA/NCI NIH HHS/United States
GR  - P50 CA70907-05/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (PYCARD protein, human)
RN  - 0 (Proteins)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis
MH  - Base Sequence
MH  - Breast Neoplasms/*genetics/metabolism
MH  - CARD Signaling Adaptor Proteins
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism
MH  - Carcinoma, Small Cell/*genetics/metabolism
MH  - Case-Control Studies
MH  - CpG Islands
MH  - Cytoskeletal Proteins
MH  - DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors/genetics/metabolism
MH  - *DNA Methylation
MH  - DNA, Neoplasm/genetics
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lung Neoplasms/*genetics/metabolism
MH  - Lymphocytes/blood/metabolism
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Proteins/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
EDAT- 2003/06/12 05:00
MHDA- 2003/08/09 05:00
CRDT- 2003/06/12 05:00
PHST- 2003/06/12 05:00 [pubmed]
PHST- 2003/08/09 05:00 [medline]
PHST- 2003/06/12 05:00 [entrez]
AID - 10.1002/ijc.11206 [doi]
PST - ppublish
SO  - Int J Cancer. 2003 Aug 20;106(2):198-204. doi: 10.1002/ijc.11206.