CpG island methylation and expression of tumour-associated genes in lung carcinoma.
In this study, microarray analysis was used to identify tumour-related genes that were down regulated in lung carcinoma. The promoter sequences of the identified genes were analysed for methylation patterns. In lung cancer cell lines, CpG island methylation was frequently detected for TIMP4 (64%), SOX18 (73%), EGF-like domain 7 (56%), CD105 (71%), SEMA2 (55%), RASSF1A (71%), p16 (56%) SLIT2 (100%) and TIMP3 (29%). Methylation was however rarely observed in cell lines for SLIT3 (18%) and DLC1 (18%). In primary lung tumours, methylation of TIMP4 (94%), SOX18 (100%), EGF-like domain 7 (100%), CD105 (69%), SEMA2 (93%), DLC1 (61%), RASSF1A (44%), p16 (47%), SLIT2 (100%) and TIMP3 (13%) was also detected. Methylation of several CpG islands was frequently found in normal lung tissue of cancer patients and this may have been attributed to epigenetic field defect and/or infiltrating tumour cells. Interestingly, inactivation of RASSF1A and p16 correlated well with an extended smoking habit (P=0.02), and exposure to asbestos (P=0.017) or squamous cell carcinoma (P=0.011), respectively. These results have identified genes whose aberrant promoter methylation could play a crucial role in the malignancy of lung carcinoma.
Dammann
Reinhard
R
AWG Tumour Genetics of the Medical Faculty, Martin-Luther-University, Halle-Wittenberg, 06097 Halle/Saale, Germany. reinhard.dammann@medizin.uni-halle.de
Strunnikova
Maria
M
Schagdarsurengin
Undraga
U
Rastetter
Matthias
M
Papritz
Mirko
M
Hattenhorst
Uwe E
UE
Hofmann
Hans-Stefan
HS
Silber
Rolf-Edgar
RE
Burdach
Stefan
S
Hansen
Gesine
G
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000097792:Tissue Inhibitor of Metalloproteinase-4
D012334:RNA, Neoplasm; D019714:Tissue Inhibitor of Metalloproteinases; D025521:Tumor Suppressor Proteins; D000097792:Tissue Inhibitor of Metalloproteinase-4; C411762:RASSF1 protein, human